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19aa10c0578e34dbdd8fe0d66c8f483977fce22f | wikidoc | STARD4 | STARD4
StAR-related lipid transfer protein 4 (STARD4) is a soluble protein involved in cholesterol transport. It can transfer up to 7 sterol molecules per minute between artificial membranes.
# Function
STARD4 may regulate cholesterol levels in many cells, including in the liver. STARD4 has specifically been linked to the movement of cholesterol to the endoplasmic reticulum. The protein is associated with the endoplasmic reticulum and lipid droplets. Increases in the protein relate to cell stress.
High levels of STARD4 increases the synthesis of bile acids and cholesterol esters in liver hepatocytes. Reductions in cholesterol synthesis by cells increase STARD4 levels while StarD4 declines in mice fed a high cholesterol diet.
Increases in levels of either master gene regulator SREBP-1a or SREBP2, which both promote the production of proteins involved in cholesterol synthesis, increase StarD4 levels in mouse liver. Conversely, increased STARD4 increases active SREBP2 levels.
Loss of the protein in mice has little effect. Mice without functional STARD4 weigh less and females tend to have lower cholesterol profiles. The most dramatic change observed to date is a reduction in NPC-1, a protein involved in bringing cholesterol into cells.
# Structure
The protein is 205 amino acids long in the human (224 in the mouse) and almost entirely consists of a StAR-related transfer (START) domain. It also lends its name to the subgroup of START domain proteins it is part of, StarD4. This subfamily includes STARD5 and STARD6 and is closely related to the StarD1/D3 group. | STARD4
StAR-related lipid transfer protein 4 (STARD4) is a soluble protein involved in cholesterol transport. It can transfer up to 7 sterol molecules per minute between artificial membranes.[1]
# Function
STARD4 may regulate cholesterol levels in many cells, including in the liver. STARD4 has specifically been linked to the movement of cholesterol to the endoplasmic reticulum. The protein is associated with the endoplasmic reticulum and lipid droplets.[2] Increases in the protein relate to cell stress.[3]
High levels of STARD4 increases the synthesis of bile acids and cholesterol esters in liver hepatocytes.[4] Reductions in cholesterol synthesis by cells increase STARD4 levels while StarD4 declines in mice fed a high cholesterol diet.[5][6]
Increases in levels of either master gene regulator SREBP-1a or SREBP2, which both promote the production of proteins involved in cholesterol synthesis, increase StarD4 levels in mouse liver.[7] Conversely, increased STARD4 increases active SREBP2 levels.
Loss of the protein in mice has little effect.[8] Mice without functional STARD4 weigh less and females tend to have lower cholesterol profiles. The most dramatic change observed to date is a reduction in NPC-1, a protein involved in bringing cholesterol into cells.
# Structure
The protein is 205 amino acids long in the human (224 in the mouse) and almost entirely consists of a StAR-related transfer (START) domain. It also lends its name to the subgroup of START domain proteins it is part of, StarD4. This subfamily includes STARD5 and STARD6 and is closely related to the StarD1/D3 group. | https://www.wikidoc.org/index.php/STARD4 | |
9bcee925d7e85bcbbcea65b2699584b25d3a45cd | wikidoc | STARD5 | STARD5
StAR-related lipid transfer protein 5 is a protein that in humans is encoded by the STARD5 gene. The protein is a 213 amino acids long, consisting almost entirely of a StAR-related transfer (START) domain. It is also part of the StarD4 subfamily of START domain proteins, sharing 34% sequence identity with STARD4.
# Function
The protein is most prevalent in the kidney and the liver where it is found in Kupffer cells. STARD5 binds both cholesterol and 25-hydroxycholesterol and appears to function to redistribute cholesterol to the endoplasmic reticulum with which the protein associates and/or the plasma membrane. Increased levels of StarD5 increase free cholesterol in the cell.
Cholesterol homeostasis is regulated, at least in part, by sterol regulatory element (SRE)-binding proteins (e.g., SREBP1) and by liver X receptors (e.g., LXRA). Upon sterol depletion, LXRs are inactive and SREBPs are cleaved, after which they bind promoter SREs and activate genes involved in cholesterol biosynthesis and uptake. Sterol transport is mediated by vesicles or by soluble protein carriers, such as steroidogenic acute regulatory protein (STAR). STAR is homologous to a family of proteins containing a 200- to 210-amino acid STAR-related lipid transfer (START) domain, including STARD5.
# Model organisms
Model organisms have been used in the study of STARD5 function. A conditional knockout mouse line, called Stard5tm1a(KOMP)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty four tests were carried out on homozygous mutant mice and one significant abnormality was observed: abnormal vertebral transverse processes. | STARD5
StAR-related lipid transfer protein 5 is a protein that in humans is encoded by the STARD5 gene.[1][2] The protein is a 213 amino acids long, consisting almost entirely of a StAR-related transfer (START) domain. It is also part of the StarD4 subfamily of START domain proteins, sharing 34% sequence identity with STARD4.
# Function
The protein is most prevalent in the kidney and the liver where it is found in Kupffer cells.[1][3] STARD5 binds both cholesterol and 25-hydroxycholesterol and appears to function to redistribute cholesterol to the endoplasmic reticulum with which the protein associates and/or the plasma membrane.[1][4][5] Increased levels of StarD5 increase free cholesterol in the cell.[4]
Cholesterol homeostasis is regulated, at least in part, by sterol regulatory element (SRE)-binding proteins (e.g., SREBP1) and by liver X receptors (e.g., LXRA). Upon sterol depletion, LXRs are inactive and SREBPs are cleaved, after which they bind promoter SREs and activate genes involved in cholesterol biosynthesis and uptake. Sterol transport is mediated by vesicles or by soluble protein carriers, such as steroidogenic acute regulatory protein (STAR). STAR is homologous to a family of proteins containing a 200- to 210-amino acid STAR-related lipid transfer (START) domain, including STARD5.[1][2]
# Model organisms
Model organisms have been used in the study of STARD5 function. A conditional knockout mouse line, called Stard5tm1a(KOMP)Wtsi[11][12] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[13][14][15]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[9][16] Twenty four tests were carried out on homozygous mutant mice and one significant abnormality was observed: abnormal vertebral transverse processes.[9] | https://www.wikidoc.org/index.php/STARD5 | |
323df615bcc8b3bd0cbf0b01edc12e4155378918 | wikidoc | STARD7 | STARD7
StAR-related lipid transfer domain protein 7 (STARD7) or gestational trophoblastic tumor gene-1 (GTT1) is a lipid transporter that specifically binds and transports phosphatidylcholine between membranes.
# Function and tissue distribution
StarD7 is found in the cytosol and associated with the mitochondrion. When overproduced in the cell, mitochondrial levels of phosphatidylcholine rise. High levels of the protein are found in tumor cells compared to normal cells, suggesting a role in cell proliferation.
# Structure
There are two forms of StarD7: StarD7-I and StarD7-II. The former is 295 amino acids long. StarD7-I possesses an additional 75 amino acids at its amino-terminus, which form a signaling sequence that targets it to the outer membrane of the mitochondrion.
StarD7 contains a StAR-related transfer domain (START), from which it derives its name. Moreover, the protein is a member of the predominantly phosphatidylcholine transporter subfamily of START proteins, the StarD2 subfamily. It shares 25% sequence identity with StarD2. | STARD7
StAR-related lipid transfer domain protein 7 (STARD7) or gestational trophoblastic tumor gene-1 (GTT1) is a lipid transporter that specifically binds and transports phosphatidylcholine between membranes.[1]
# Function and tissue distribution
StarD7 is found in the cytosol and associated with the mitochondrion.[1] When overproduced in the cell, mitochondrial levels of phosphatidylcholine rise.[1] High levels of the protein are found in tumor cells compared to normal cells, suggesting a role in cell proliferation.[2]
# Structure
There are two forms of StarD7: StarD7-I and StarD7-II. The former is 295 amino acids long. StarD7-I possesses an additional 75 amino acids at its amino-terminus, which form a signaling sequence that targets it to the outer membrane of the mitochondrion.[1]
StarD7 contains a StAR-related transfer domain (START), from which it derives its name. Moreover, the protein is a member of the predominantly phosphatidylcholine transporter subfamily of START proteins, the StarD2 subfamily. It shares 25% sequence identity with StarD2.[1] | https://www.wikidoc.org/index.php/STARD7 | |
4d6ffbea2d2e747d2870afdcecb3eafa44eed1bd | wikidoc | STARD8 | STARD8
StAR-related lipid transfer domain protein 8 (STARD8) also known as deleted in liver cancer 3 protein (DLC-3) is a protein that in humans is encoded by the STARD8 gene and is a member of the DLC family.
# Structure and function
The protein is 1103 amino acids long, which like other DLC proteins consists of a sterile alpha motif (SAM), RhoGAP and a StAR-related lipid-transfer (START) domains.
The protein is a Rho GTPase-activating protein (GAP), a type of protein that regulates members of the Rho family of GTPases. STARD8 is characterized as activating Rho GTPases. Its expression inhibits the growth of human breast and prostate cancer cells in culture.
# Tissue distribution and pathology
The protein is expressed in tissues throughout the body, but is absent or reduced in many kinds of tumor cells.
While there are no known disorders caused by STARD8, partial loss of the STARD8 gene occurs in cases of craniofrontonasal syndrome where the EFNB1 gene (which causes the syndrome) is completely deleted.
# Model organisms
Model organisms have been used in the study of STARD8 function. A conditional knockout mouse line called Stard8tm1b(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping | STARD8
StAR-related lipid transfer domain protein 8 (STARD8) also known as deleted in liver cancer 3 protein (DLC-3) is a protein that in humans is encoded by the STARD8 gene[1][2] and is a member of the DLC family.
# Structure and function
The protein is 1103 amino acids long, which like other DLC proteins consists of a sterile alpha motif (SAM), RhoGAP and a StAR-related lipid-transfer (START) domains.[3]
The protein is a Rho GTPase-activating protein (GAP), a type of protein that regulates members of the Rho family of GTPases. STARD8 is characterized as activating Rho GTPases. Its expression inhibits the growth of human breast and prostate cancer cells in culture.[3]
# Tissue distribution and pathology
The protein is expressed in tissues throughout the body, but is absent or reduced in many kinds of tumor cells.[3]
While there are no known disorders caused by STARD8, partial loss of the STARD8 gene occurs in cases of craniofrontonasal syndrome where the EFNB1 gene (which causes the syndrome) is completely deleted.[4][5]
# Model organisms
Model organisms have been used in the study of STARD8 function. A conditional knockout mouse line called Stard8tm1b(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[6] Male and female animals underwent a standardized phenotypic screen[7] to determine the effects of deletion.[8][9][10][11] Additional screens performed: - In-depth immunological phenotyping[12] | https://www.wikidoc.org/index.php/STARD8 | |
9138ef9ad9213fafb1c036dd0121aaff74d4b2c6 | wikidoc | STAT5A | STAT5A
Signal transducer and activator of transcription 5A is a protein that in humans is encoded by the STAT5A gene. STAT5A orthologs have been identified in several placentals for which complete genome data are available.
# Structure
STAT5a shares the same six functional domains as the other members of the STAT family. It contains 20 amino acids unique to its C-terminal domain and is 96% similar to its homolog, STAT5b. The six functional domains and their corresponding amino acid positions are as follows:
- N-Terminal domain (aa1-144): stabilized interactions to form tetramers
- Coiled-coil domain (aa145-330): interacts with chaperones and facilitates protein-protein interactions for transcriptional regulation
- DNA binding domain (aa331-496): permits binding to consensus gamma-interferon activation sequence (GAS)
- Linker domain (aa497-592): stabilizes DNA binding
- Src Homology 2 domain (aa593-685): mediates receptor-specific recruitment and STAT dimerization via phosphorylated tyrosine residue
- Transcriptional activation domain (aa702-794): interacts with critical co-activators
In addition to the six functional domains, specific amino acids have been identified as key mediators of STAT5a function. Phosphorylation of tyrosine 694 and glycosylation of threonine 92 are important for STAT5a activity. Mutation of serine 710 to phenylalanine results in constitutive activation.
# Function
The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is activated by, and mediates the responses of many cell ligands, such as IL2, IL3, IL7 GM-CSF, erythropoietin, thrombopoietin, and different growth hormones. Activation of this protein in myeloma and lymphoma associated with a TEL/JAK2 gene fusion is independent of cell stimulus and has been shown to be essential for the tumorigenesis. The mouse counterpart of this gene is found to induce the expression of BCL2L1/BCL-X(L), which suggests the antiapoptotic function of this gene in cells. It also transduces prolactin signals to the milk protein genes and is necessary for mammary gland development.
# STAT5a and cancer
Many studies have indicated a key role of STAT5a in leukemia, breast, colon, head and neck, and prostate cancer. Until recently, the unique characteristics and function of STAT5a in these cancers have not been delineated from STAT5b, and more research into their differential behavior is warranted. Because of its integral role in immune cell development, STAT5a may contribute to tumor development by compromising immune surveillance.
STAT5a expression has been studied closely in prostate and breast cancer, and has only recently shown some promise with colorectal and head and neck cancer. Unphosphorylated or inactive STAT5a may suppress tumor growth in colorectal cancer and active STAT5a expression in premalignant and tumor lesions has shown potential as a prognostic marker in oral squamous cell carcinoma.
## Prostate Cancer
STAT5a is involved in the maintenance of integrated prostate epithelial structure and has been shown to be critical for cell viability and tumor growth. Stat5a/b is persistently active in prostate cancer cells and inhibition of STAT5a/b has resulted in large scale apoptotic death, although the specific role of STAT5a and distribution of activity remains largely unknown. Prolactin has been known to activate the JAK2-STAT5a/b pathway in both normal and malignant prostate epithelium, but again, the specific activity of STAT5a remains unknown.
## Breast Cancer
In normal tissue, STAT5a mediates effects of prolactin in mammary glands. In breast cancer, STAT5a signaling is important for maintain tumor differentiation and suppressing disease progression. Studies originally showed a correlation between high STAT5a expression and tumor differentiation in mice models, but histopathological analysis of human breast cancer tissue has shown a different trend. It was shown that low nuclear levels of STAT5a was associated with unfavorable clinical outcomes and cancer progression independent of STAT5b expression. High STAT5a was suggested to be an inhibitor of invasion and metastasis and therefore an indicator of favorable clinical outcomes. Because of these trends, it has been proposed as a predictor of response to therapies such as anti-estrogen treatment.
## Therapeutic Treatment Approaches
Because the specific activity of STAT5a has not been extensively investigated, most potential therapeutic treatments aim to target STAT5a/b. So far, the only reported potential therapeutic benefit specific to STAT5a has been in colorectal cancer. Inhibition of STAT5a alone would not effect colorectal cancer cells, but when combined with chemotherapies such as cisplatin, it could increase the chemosensitivity of the cancer cells to the drugs. Therapy schemes currently focus on STAT5a/b, targeting and inhibiting different mediators of the JAK2-STAT5 pathway.
# Interactions
STAT5A has been shown to interact with:
- CRKL,
- Epidermal growth factor receptor,
- ERBB4,
- Erythropoietin receptor,
- Janus kinase 1,
- Janus kinase 2,
- MAPK1
- NMI, and
- PTPN11.
- CBX5, | STAT5A
Signal transducer and activator of transcription 5A is a protein that in humans is encoded by the STAT5A gene.[1][2] STAT5A orthologs [3] have been identified in several placentals for which complete genome data are available.
# Structure
STAT5a shares the same six functional domains as the other members of the STAT family. It contains 20 amino acids unique to its C-terminal domain and is 96% similar to its homolog, STAT5b. The six functional domains and their corresponding amino acid positions are as follows:
- N-Terminal domain (aa1-144): stabilized interactions to form tetramers
- Coiled-coil domain (aa145-330): interacts with chaperones and facilitates protein-protein interactions for transcriptional regulation
- DNA binding domain (aa331-496): permits binding to consensus gamma-interferon activation sequence (GAS)
- Linker domain (aa497-592): stabilizes DNA binding
- Src Homology 2 domain (aa593-685): mediates receptor-specific recruitment and STAT dimerization via phosphorylated tyrosine residue
- Transcriptional activation domain (aa702-794): interacts with critical co-activators
In addition to the six functional domains, specific amino acids have been identified as key mediators of STAT5a function. Phosphorylation of tyrosine 694 and glycosylation of threonine 92 are important for STAT5a activity. Mutation of serine 710 to phenylalanine results in constitutive activation.[4][5]
# Function
The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is activated by, and mediates the responses of many cell ligands, such as IL2, IL3, IL7 GM-CSF, erythropoietin, thrombopoietin, and different growth hormones. Activation of this protein in myeloma and lymphoma associated with a TEL/JAK2 gene fusion is independent of cell stimulus and has been shown to be essential for the tumorigenesis. The mouse counterpart of this gene is found to induce the expression of BCL2L1/BCL-X(L), which suggests the antiapoptotic function of this gene in cells.[6] It also transduces prolactin signals to the milk protein genes and is necessary for mammary gland development.[7]
# STAT5a and cancer
Many studies have indicated a key role of STAT5a in leukemia, breast, colon, head and neck, and prostate cancer.[4][7][8][9] Until recently, the unique characteristics and function of STAT5a in these cancers have not been delineated from STAT5b, and more research into their differential behavior is warranted. Because of its integral role in immune cell development, STAT5a may contribute to tumor development by compromising immune surveillance.[7]
STAT5a expression has been studied closely in prostate and breast cancer, and has only recently shown some promise with colorectal and head and neck cancer. Unphosphorylated or inactive STAT5a may suppress tumor growth in colorectal cancer and active STAT5a expression in premalignant and tumor lesions has shown potential as a prognostic marker in oral squamous cell carcinoma.[7][10]
## Prostate Cancer
STAT5a is involved in the maintenance of integrated prostate epithelial structure and has been shown to be critical for cell viability and tumor growth. Stat5a/b is persistently active in prostate cancer cells and inhibition of STAT5a/b has resulted in large scale apoptotic death, although the specific role of STAT5a and distribution of activity remains largely unknown.[4] Prolactin has been known to activate the JAK2-STAT5a/b pathway in both normal and malignant prostate epithelium, but again, the specific activity of STAT5a remains unknown.[5]
## Breast Cancer
In normal tissue, STAT5a mediates effects of prolactin in mammary glands. In breast cancer, STAT5a signaling is important for maintain tumor differentiation and suppressing disease progression. Studies originally showed a correlation between high STAT5a expression and tumor differentiation in mice models, but histopathological analysis of human breast cancer tissue has shown a different trend. It was shown that low nuclear levels of STAT5a was associated with unfavorable clinical outcomes and cancer progression independent of STAT5b expression. High STAT5a was suggested to be an inhibitor of invasion and metastasis and therefore an indicator of favorable clinical outcomes. Because of these trends, it has been proposed as a predictor of response to therapies such as anti-estrogen treatment.[8][11]
## Therapeutic Treatment Approaches
Because the specific activity of STAT5a has not been extensively investigated, most potential therapeutic treatments aim to target STAT5a/b. So far, the only reported potential therapeutic benefit specific to STAT5a has been in colorectal cancer. Inhibition of STAT5a alone would not effect colorectal cancer cells, but when combined with chemotherapies such as cisplatin, it could increase the chemosensitivity of the cancer cells to the drugs.[9] Therapy schemes currently focus on STAT5a/b, targeting and inhibiting different mediators of the JAK2-STAT5 pathway.[4]
# Interactions
STAT5A has been shown to interact with:
- CRKL,[12]
- Epidermal growth factor receptor,[13][14]
- ERBB4,[13][15]
- Erythropoietin receptor,[16]
- Janus kinase 1,[17]
- Janus kinase 2,[17][18]
- MAPK1[19][20]
- NMI,[21] and
- PTPN11.[22][23]
- CBX5,[10] | https://www.wikidoc.org/index.php/STAT5A | |
66a627a9abf40c7483704c4a4d243f275856c628 | wikidoc | STEAP3 | STEAP3
Metalloreductase STEAP3 is an enzyme that in humans is encoded by the STEAP3 gene.
STEAP3 is a metalloreductase, capable of coverting iron from an insoluble ferric (Fe3+) to a soluble ferrous (Fe2+) form.
STEAP3 and other STEAP protein, with the exception of STEAP1, are predicted to contain a Di-nucleotide binding domain (Rossmann Fold). This has been shown using X-ray crystallography in the cases of STEAP3 and STEAP4 (PDB: 2VNS, 2VQ3 and 2YJZ).
# Interactions
STEAP3 has been shown to interact with BNIP3L and PKMYT1. | STEAP3
Metalloreductase STEAP3 is an enzyme that in humans is encoded by the STEAP3 gene.[1][2]
STEAP3 is a metalloreductase, capable of coverting iron from an insoluble ferric (Fe3+) to a soluble ferrous (Fe2+) form.[3]
STEAP3 and other STEAP protein, with the exception of STEAP1, are predicted to contain a Di-nucleotide binding domain (Rossmann Fold). This has been shown using X-ray crystallography in the cases of STEAP3 and STEAP4 (PDB: 2VNS, 2VQ3 and 2YJZ).[4][5]
# Interactions
STEAP3 has been shown to interact with BNIP3L[1] and PKMYT1.[1] | https://www.wikidoc.org/index.php/STEAP3 | |
8e32e9199d862aaafba8eccb28d2de14de7dad49 | wikidoc | STXBP1 | STXBP1
Syntaxin-binding protein 1 (also known as Munc18-1) is a protein that in humans is encoded by the STXBP1 gene. This gene encodes a syntaxin-binding protein. The encoded protein appears to play a role in release of neurotransmitters via regulation of syntaxin, a transmembrane attachment protein receptor. Mutations in this gene have been associated with infantile epileptic encephalopathy-4.
# Structure
The STXBP1 gene is located on the q arm of chromosome 9 in position 34.11 and has 20 exons spanning 80,510 base pairs. The encoded protein is a peripheral membrane protein located in the cytosol. In the retina and cerebellum, an alternatively spliced transcript variant is expressed, containing an additional exon and totaling 603 amino acids. Alternative splicing can produce an isoform with exon 19 and an isoform without.
# Function
The encoded protein may participate in the regulation of synaptic vesicle docking and fusion, possibly through interaction with GTP-binding proteins. It is essential for neurotransmission and binds syntaxin, a component of the synaptic vesicle fusion machinery probably in a 1:1 ratio. It can interact with syntaxins 1, 2, and 3 but not syntaxin 4 and may play a role in determining the specificity of intracellular fusion reactions. This protein functions in a late stage of the intracellular membrane fusion process of exocytosis. Dissociation of this protein from syntaxin determines the kinetics of postfusion events. This protein is essential for presynpatic vesicle release and is rapidly phosphorylated by protein kinase C upon neuronal depolarization. The protein participates in the secretory pathway between the Golgi apparatus and cell membrane.
# Clinical Significance
## Epileptic Encephalopathy
Mutations in the STXBP1 cause Early Infantile Epileptic Encephalopathy Type 4 (EIEE4), a severe form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Affected individuals have neonatal or infantile onset of seizures, profound mental retardation, and MRI evidence of brain hypomyelination. Inheritance of EIEE4 is autosomal dominant.
This gene was initially discovered in 2008 as cause for Ohtahara Syndrome. Ever since, it has become one of the most prominent genes for epileptic encephalopathies so far.
## Expression
In melanocytic cells STXBP1 gene expression may be regulated by MITF.
The STXBP1 gene is expressed in the brain and spinal cord and highly enriched in axons. Expression of this protein is highest in the retina and cerebellum.
# Interactions
The encoded protein binds SYTL4. STXBP1 has been shown to interact with STX2, STX4 and STX1A. | STXBP1
Syntaxin-binding protein 1 (also known as Munc18-1) is a protein that in humans is encoded by the STXBP1 gene.[1] This gene encodes a syntaxin-binding protein. The encoded protein appears to play a role in release of neurotransmitters via regulation of syntaxin, a transmembrane attachment protein receptor. Mutations in this gene have been associated with infantile epileptic encephalopathy-4.[2]
# Structure
The STXBP1 gene is located on the q arm of chromosome 9 in position 34.11 and has 20 exons spanning 80,510 base pairs.[2] The encoded protein is a peripheral membrane protein located in the cytosol.[3][4] In the retina and cerebellum, an alternatively spliced transcript variant is expressed, containing an additional exon and totaling 603 amino acids.[5] Alternative splicing can produce an isoform with exon 19 and an isoform without.[6][7]
# Function
The encoded protein may participate in the regulation of synaptic vesicle docking and fusion, possibly through interaction with GTP-binding proteins. It is essential for neurotransmission and binds syntaxin, a component of the synaptic vesicle fusion machinery probably in a 1:1 ratio. It can interact with syntaxins 1, 2, and 3 but not syntaxin 4 and may play a role in determining the specificity of intracellular fusion reactions.[3][4] This protein functions in a late stage of the intracellular membrane fusion process of exocytosis. Dissociation of this protein from syntaxin determines the kinetics of postfusion events.[8] This protein is essential for presynpatic vesicle release and is rapidly phosphorylated by protein kinase C upon neuronal depolarization.[9] The protein participates in the secretory pathway between the Golgi apparatus and cell membrane.[10][7]
# Clinical Significance
## Epileptic Encephalopathy
Mutations in the STXBP1 cause Early Infantile Epileptic Encephalopathy Type 4 (EIEE4), a severe form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Affected individuals have neonatal or infantile onset of seizures, profound mental retardation, and MRI evidence of brain hypomyelination. Inheritance of EIEE4 is autosomal dominant.[3][4]
This gene was initially discovered in 2008 as cause for Ohtahara Syndrome. Ever since, it has become one of the most prominent genes for epileptic encephalopathies so far.[11]
## Expression
In melanocytic cells STXBP1 gene expression may be regulated by MITF.[12]
The STXBP1 gene is expressed in the brain and spinal cord and highly enriched in axons.[3][4] Expression of this protein is highest in the retina and cerebellum.[5][7]
# Interactions
The encoded protein binds SYTL4.[3][4] STXBP1 has been shown to interact with STX2,[13][14] STX4[13][14] and STX1A.[14][15][16][17][18] | https://www.wikidoc.org/index.php/STXBP1 | |
9042df7b29a28917029d3aac05524be6b63bf5ae | wikidoc | SUCLA2 | SUCLA2
Succinyl-CoA ligase subunit beta, mitochondrial (SUCLA2), also known as ADP-forming succinyl-CoA synthetase (SCS-A), is an enzyme that in humans is encoded by the SUCLA2 gene on chromosome 13.
Succinyl-CoA synthetase (SCS) is a mitochondrial matrix enzyme that acts as a heterodimer, being composed of an invariant alpha subunit and a substrate-specific beta subunit. The protein encoded by this gene is an ATP-specific SCS beta subunit that dimerizes with the SCS alpha subunit to form SCS-A, an essential component of the tricarboxylic acid cycle. SCS-A hydrolyzes ATP to convert succinyl-CoA to succinate. Defects in this gene are a cause of myopathic mitochondrial DNA depletion syndrome. A pseudogene of this gene has been found on chromosome 6.
# Structure
SCS, also known as succinyl CoA ligase (SUCL), is a heterodimer composed of a catalytic α subunit encoded by the SUCLG1 gene and a β subunit encoded by either the SUCLA2 gene or the SUCLG2 gene, which determines the enzyme specificity for either ADP or GDP. SUCLA2 is the SCS variant containing the SUCLA2-encoded β subunit. Amino acid sequence alignment of the two β subunit types reveals a homology of ~50% identity, with specific regions conserved throughout the sequences.
SUCLA2 is located on chromosome 13 and contains 13 exons.
# Function
As a subunit of SCS, SUCLA2 is a mitochondrial matrix enzyme that catalyzes the reversible conversion of succinyl-CoA to succinate and acetoacetyl CoA, accompanied by the substrate-level phosphorylation of ADP to ATP, as a step in the tricarboxylic acid (TCA) cycle. The ATP generated is then consumed in catabolic pathways. Since substrate-level phosphorylation does not require oxygen for ATP production, this reaction can rescue cells from cytosolic ATP depletion during ischemia. The reverse reaction generates succinyl-CoA from succinate to fuel ketone body and heme synthesis.
While SCS is ubiquitously expressed, SUCLA2 is predominantly expressed in catabolic tissues reliant on ATP as their main energy source, including heart, brain, and skeletal muscle. Within the brain, SUCLA2 is found exclusively in neurons; meanwhile, both SUCLA2 and SUCLG2 are absent in astrocytes, microglia, and oligodendrocytes. In order to acquire succinate to continue the TCA cycle, these cells may instead synthesize succinate through GABA metabolism of α-ketoglutarate or ketone body metabolism of succinyl-CoA.
# Clinical significance
Mutations in the SUCLA2 gene are associated with mitochondrial DNA (mtDNA) depletion syndrome. Symptoms include early onset low muscle tone, severe muscular atrophy, scoliosis, movement disorders such as dystonia and hyperkinesia, epilepsy, and growth retardation. Because succinic acid can not be made from succinyl coa, treatment is with oral succinic acid, which allows the krebs cycle, and electron transport chain to function correctly. Other treatments are managing symptoms and includes exercises to promote mobility, respiratory assistance, baclofen to treat dystonia and hyperkinesia, and antiepileptic drugs for seizures.
There is a relatively high incidence of a specific SUCLA2 mutation in the Faroe Islands due to a founder effect. This particular mutation is often associated with early lethality. Two additional founder mutations in have been discovered in the Scandinavian population, in addition to the known SUCLA2 founder mutation in the Faroe Islands. These patients show a higher variability in outcomes with a number of patients with SUCLA2 missense mutation surviving into adulthood. This variability suggests that SUCLA2 missense mutations may be associated with residual enzyme activity.
Coenzyme Q10 and antioxidants have been used to treat mitochondrial DNA depletion syndrome but there is currently no evidence that these treatments result in clinical benefit.
Mutations in the SUCLA2 gene leading to SUCLA2 deficiency result in Leigh's or a Leigh-like syndrome with onset of severe hypotonia, muscular atrophy, sensorineural hearing impairment, and often death in early childhood. | SUCLA2
Succinyl-CoA ligase [ADP-forming] subunit beta, mitochondrial (SUCLA2), also known as ADP-forming succinyl-CoA synthetase (SCS-A), is an enzyme that in humans is encoded by the SUCLA2 gene on chromosome 13.[1][2][3]
Succinyl-CoA synthetase (SCS) is a mitochondrial matrix enzyme that acts as a heterodimer, being composed of an invariant alpha subunit and a substrate-specific beta subunit. The protein encoded by this gene is an ATP-specific SCS beta subunit that dimerizes with the SCS alpha subunit to form SCS-A, an essential component of the tricarboxylic acid cycle. SCS-A hydrolyzes ATP to convert succinyl-CoA to succinate. Defects in this gene are a cause of myopathic mitochondrial DNA depletion syndrome. A pseudogene of this gene has been found on chromosome 6. [provided by RefSeq, Jul 2008][2]
# Structure
SCS, also known as succinyl CoA ligase (SUCL), is a heterodimer composed of a catalytic α subunit encoded by the SUCLG1 gene and a β subunit encoded by either the SUCLA2 gene or the SUCLG2 gene, which determines the enzyme specificity for either ADP or GDP. SUCLA2 is the SCS variant containing the SUCLA2-encoded β subunit.[4][5][6] Amino acid sequence alignment of the two β subunit types reveals a homology of ~50% identity, with specific regions conserved throughout the sequences.[1]
SUCLA2 is located on chromosome 13 and contains 13 exons.[2]
# Function
As a subunit of SCS, SUCLA2 is a mitochondrial matrix enzyme that catalyzes the reversible conversion of succinyl-CoA to succinate and acetoacetyl CoA, accompanied by the substrate-level phosphorylation of ADP to ATP, as a step in the tricarboxylic acid (TCA) cycle.[4][5][6] The ATP generated is then consumed in catabolic pathways.[5] Since substrate-level phosphorylation does not require oxygen for ATP production, this reaction can rescue cells from cytosolic ATP depletion during ischemia.[6] The reverse reaction generates succinyl-CoA from succinate to fuel ketone body and heme synthesis.[4][6]
While SCS is ubiquitously expressed, SUCLA2 is predominantly expressed in catabolic tissues reliant on ATP as their main energy source, including heart, brain, and skeletal muscle.[1][3][6] Within the brain, SUCLA2 is found exclusively in neurons; meanwhile, both SUCLA2 and SUCLG2 are absent in astrocytes, microglia, and oligodendrocytes. In order to acquire succinate to continue the TCA cycle, these cells may instead synthesize succinate through GABA metabolism of α-ketoglutarate or ketone body metabolism of succinyl-CoA.[5][6]
# Clinical significance
Mutations in the SUCLA2 gene are associated with mitochondrial DNA (mtDNA) depletion syndrome.[7][8] Symptoms include early onset low muscle tone, severe muscular atrophy, scoliosis, movement disorders such as dystonia and hyperkinesia, epilepsy, and growth retardation. Because succinic acid can not be made from succinyl coa, treatment is with oral succinic acid, which allows the krebs cycle, and electron transport chain to function correctly. Other treatments are managing symptoms and includes exercises to promote mobility, respiratory assistance, baclofen to treat dystonia and hyperkinesia, and antiepileptic drugs for seizures.[7][9]
There is a relatively high incidence of a specific SUCLA2 mutation in the Faroe Islands due to a founder effect. This particular mutation is often associated with early lethality.[10] Two additional founder mutations in have been discovered in the Scandinavian population, in addition to the known SUCLA2 founder mutation in the Faroe Islands.[11] These patients show a higher variability in outcomes with a number of patients with SUCLA2 missense mutation surviving into adulthood. This variability suggests that SUCLA2 missense mutations may be associated with residual enzyme activity.[11]
Coenzyme Q10 and antioxidants have been used to treat mitochondrial DNA depletion syndrome but there is currently no evidence that these treatments result in clinical benefit.[9][12]
Mutations in the SUCLA2 gene leading to SUCLA2 deficiency result in Leigh's or a Leigh-like syndrome with onset of severe hypotonia, muscular atrophy, sensorineural hearing impairment, and often death in early childhood.[4][6] | https://www.wikidoc.org/index.php/SUCLA2 | |
a54519226aae36e7a6fc8564136dc7ba4291b594 | wikidoc | SUCLG1 | SUCLG1
Succinyl-CoA ligase subunit alpha, mitochondrial is an enzyme that in humans is encoded by the SUCLG1 gene.
# Structure
The enzyme encoded by SUCLG1 can exist in either a phosphorylated form or a dephosphorylated form. In the dephosphorylated structure, a phosphate ion works in coordination with a histidine residue in the active site and the two alpha helices, one contributed by each subunit of the alphabeta-dimer to stabilize the structure. One of the alpha helices contains amino acids, the modification of which result in conformational changes that accommodate either the bound phosphoryl group or the free phosphate ion.
# Function
This gene encodes the alpha subunit of the heterodimeric enzyme succinate coenzyme A ligase. This enzyme is targeted to the mitochondria and catalyzes the conversion of succinyl CoA and ADP or GDP to succinate and ATP or GTP. Mutations in this gene are the cause of the metabolic disorder fatal infantile lactic acidosis and mitochondrial DNA depletion.
# Clinical significance
Succinate-CoA ligase deficiency is responsible for encephalomyopathy with mitochondrial DNA depletion and mild methylmalonic aciduria. Mutations in SUCLG1 lead to complete absence of SUCLG1 protein and are responsible for a very severe disorder with antenatal manifestations. Furthermore, it is shown that in the absence of SUCLG1 protein, no SUCLA2 protein is found in fibroblasts by western blot analysis. This result is consistent with a degradation of SUCLA2 when its heterodimer partner, SUCLG1, is absent. As mitochondrial DNA depletion in muscle is not a constant finding in SUCLG1 patients, diagnosis should not be based on it; additionally, it may be that alternative physiopathological mechanisms may be considered to explain the combined respiratory chain deficiency observed in these patients.
# Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.
- ↑ The interactive pathway map can be edited at WikiPathways: "TCACycle_WP78"..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | SUCLG1
Succinyl-CoA ligase [GDP-forming] subunit alpha, mitochondrial is an enzyme that in humans is encoded by the SUCLG1 gene.[1][2]
# Structure
The enzyme encoded by SUCLG1 can exist in either a phosphorylated form or a dephosphorylated form. In the dephosphorylated structure, a phosphate ion works in coordination with a histidine residue in the active site and the two alpha helices, one contributed by each subunit of the alphabeta-dimer to stabilize the structure. One of the alpha helices contains amino acids, the modification of which result in conformational changes that accommodate either the bound phosphoryl group or the free phosphate ion.[3]
# Function
This gene encodes the alpha subunit of the heterodimeric enzyme succinate coenzyme A ligase. This enzyme is targeted to the mitochondria and catalyzes the conversion of succinyl CoA and ADP or GDP to succinate and ATP or GTP. Mutations in this gene are the cause of the metabolic disorder fatal infantile lactic acidosis and mitochondrial DNA depletion.[4][5]
# Clinical significance
Succinate-CoA ligase deficiency is responsible for encephalomyopathy with mitochondrial DNA depletion and mild methylmalonic aciduria. Mutations in SUCLG1 lead to complete absence of SUCLG1 protein and are responsible for a very severe disorder with antenatal manifestations. Furthermore, it is shown that in the absence of SUCLG1 protein, no SUCLA2 protein is found in fibroblasts by western blot analysis. This result is consistent with a degradation of SUCLA2 when its heterodimer partner, SUCLG1, is absent.[6] As mitochondrial DNA depletion in muscle is not a constant finding in SUCLG1 patients, diagnosis should not be based on it; additionally, it may be that alternative physiopathological mechanisms may be considered to explain the combined respiratory chain deficiency observed in these patients.[5]
# Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
- ↑ The interactive pathway map can be edited at WikiPathways: "TCACycle_WP78"..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | https://www.wikidoc.org/index.php/SUCLG1 | |
e2c63b39935b9e6ba58e845cec46f070f124c583 | wikidoc | SUCLG2 | SUCLG2
Succinyl-CoA ligase subunit beta, mitochondrial is an enzyme that in humans is encoded by the SUCLG2 gene on chromosome 3.
This gene encodes a GTP-specific beta subunit of succinyl-CoA synthetase. Succinyl-CoA synthetase catalyzes the reversible reaction involving the formation of succinyl-CoA and succinate. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 5 and 12.
# Structure
SCS, also known as succinyl CoA ligase (SUCL), is a heterodimer composed of a catalytic α subunit encoded by the SUCLG1 gene and a β subunit encoded by either the SUCLA2 gene or the SUCLG2 gene, which determines the enzyme specificity for either ADP or GDP. SUCLG2 is the SCS variant containing the SUCLG2-encoded β subunit. Amino acid sequence alignment of the two β subunit types reveals a homology of ~50% identity, with specific regions conserved throughout the sequences.
SUCLG2 is located on chromosome 3 and contains 14 exons.
# Function
As a subunit of SCS, SUCLG2 is a mitochondrial matrix enzyme that catalyzes the reversible conversion of succinyl-CoA to succinate and acetoacetyl CoA, accompanied by the substrate-level phosphorylation of GDP to GTP, as a step in the tricarboxylic acid (TCA) cycle. The GTP generated is then consumed in anabolic pathways. However, since GTP is not transported through the inner mitochondrial membrane in mammals and other higher organisms, it must be recycled within the matrix. In addition, SUCLG2 may function in ATP generation in the absence of SUCLA2 by complexing with the mitochondrial nucleotide diphosphate kinase, nm23-H4, and thus compensate for SUCLA2 deficiency. The reverse reaction generates succinyl-CoA from succinate to fuel ketone body and heme synthesis.
While SCS is ubiquitously expressed, SUCLG2 is predominantly expressed in tissues involved in biosynthesis, including liver and kidney. SUCLG2 has also been detected in the microvasculature of the brain, likely to support its growth. Notably, both SUCLA2 and SUCLG2 are absent in astrocytes, microglia, and oligodendrocytes in the brain; thus, in order to acquire succinate to continue the TCA cycle, these cells may instead synthesize succinate through GABA metabolism of α-ketoglutarate or ketone body metabolism of succinyl-CoA.
# Clinical significance
Though mitochondrial DNA (mtDNA) depletion syndrome has been largely attributed to SUCLA2 deficiency, SUCLG2 may play a more crucial role in mtDNA maintenance, as it functions to compensate for SUCLA2 deficiency and its absence results in decreased mtDNA and OXPHOS-dependent growth. Moreover, no mutations in the SUCLG2 gene have been reported, indicating that such mutations are lethal and selected against.
SUCLG2 may also play a role in clearing cerebrospinal fluid amyloid-beta 1–42 (Aβ1–42) in Alzheimer's disease (AD) and, thus, reducing neuronal death. | SUCLG2
Succinyl-CoA ligase [GDP-forming] subunit beta, mitochondrial is an enzyme that in humans is encoded by the SUCLG2 gene on chromosome 3.[1]
This gene encodes a GTP-specific beta subunit of succinyl-CoA synthetase. Succinyl-CoA synthetase catalyzes the reversible reaction involving the formation of succinyl-CoA and succinate. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 5 and 12. [provided by RefSeq, Apr 2010][1]
# Structure
SCS, also known as succinyl CoA ligase (SUCL), is a heterodimer composed of a catalytic α subunit encoded by the SUCLG1 gene and a β subunit encoded by either the SUCLA2 gene or the SUCLG2 gene, which determines the enzyme specificity for either ADP or GDP. SUCLG2 is the SCS variant containing the SUCLG2-encoded β subunit.[2][3][4] Amino acid sequence alignment of the two β subunit types reveals a homology of ~50% identity, with specific regions conserved throughout the sequences.[5]
SUCLG2 is located on chromosome 3 and contains 14 exons.[1]
# Function
As a subunit of SCS, SUCLG2 is a mitochondrial matrix enzyme that catalyzes the reversible conversion of succinyl-CoA to succinate and acetoacetyl CoA, accompanied by the substrate-level phosphorylation of GDP to GTP, as a step in the tricarboxylic acid (TCA) cycle.[2][3][4][6] The GTP generated is then consumed in anabolic pathways.[3][5] However, since GTP is not transported through the inner mitochondrial membrane in mammals and other higher organisms, it must be recycled within the matrix.[4] In addition, SUCLG2 may function in ATP generation in the absence of SUCLA2 by complexing with the mitochondrial nucleotide diphosphate kinase, nm23-H4, and thus compensate for SUCLA2 deficiency.[2][4] The reverse reaction generates succinyl-CoA from succinate to fuel ketone body and heme synthesis.[2][4]
While SCS is ubiquitously expressed, SUCLG2 is predominantly expressed in tissues involved in biosynthesis, including liver and kidney.[4][5][7] SUCLG2 has also been detected in the microvasculature of the brain, likely to support its growth.[3] Notably, both SUCLA2 and SUCLG2 are absent in astrocytes, microglia, and oligodendrocytes in the brain; thus, in order to acquire succinate to continue the TCA cycle, these cells may instead synthesize succinate through GABA metabolism of α-ketoglutarate or ketone body metabolism of succinyl-CoA.[3][4]
# Clinical significance
Though mitochondrial DNA (mtDNA) depletion syndrome has been largely attributed to SUCLA2 deficiency, SUCLG2 may play a more crucial role in mtDNA maintenance, as it functions to compensate for SUCLA2 deficiency and its absence results in decreased mtDNA and OXPHOS-dependent growth.[2] Moreover, no mutations in the SUCLG2 gene have been reported, indicating that such mutations are lethal and selected against.[4]
SUCLG2 may also play a role in clearing cerebrospinal fluid amyloid-beta 1–42 (Aβ1–42) in Alzheimer's disease (AD) and, thus, reducing neuronal death.[6] | https://www.wikidoc.org/index.php/SUCLG2 | |
a1975e818dcf0a8da51b245b33d6aa5c41e61f40 | wikidoc | SUPT7L | SUPT7L
STAGA complex 65 subunit gamma is a protein that in humans is encoded by the SUPT7L gene.
# Model organisms
Model organisms have been used in the study of SUPT7L function. A conditional knockout mouse line, called Supt7ltm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty four tests were carried out on mutant mice and two significant abnormalities were observed. No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice but no further abnormalities were observed.
# Interactions
SUPT7L has been shown to interact with TAF9 and Transcription initiation protein SPT3 homolog. | SUPT7L
STAGA complex 65 subunit gamma is a protein that in humans is encoded by the SUPT7L gene.[1][2][3]
# Model organisms
Model organisms have been used in the study of SUPT7L function. A conditional knockout mouse line, called Supt7ltm1a(EUCOMM)Wtsi[9][10] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[11][12][13]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[7][14] Twenty four tests were carried out on mutant mice and two significant abnormalities were observed.[7] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice but no further abnormalities were observed.[7]
# Interactions
SUPT7L has been shown to interact with TAF9[2] and Transcription initiation protein SPT3 homolog.[2] | https://www.wikidoc.org/index.php/SUPT7L | |
454566c80f069478d4fc4c20d64cdb67cb1e8e41 | wikidoc | SYNPO2 | SYNPO2
Myopodin protein, also called Synaptopodin-2 is a protein that in humans is encoded by the SYNPO2 gene. Myopodin is expressed in cardiac, smooth muscle and skeletal muscle, and localizes to Z-disc structures.
# Structure
Myopodin is a 117.4 kDa protein composed of 1093 amino acids, although four alternatively-spliced isoforms have been described. Myopodin contains one PPXY motif, multiple PXXP motifs, and two potential nuclear localization sequences (one N-terminal and one C-terminal). PPXY motifs have been shown to mediate interactions, and PXXP motifs represent potential sites of interaction for SH3 domain-containing proteins. Myopodin contains a novel actin binding site (between amino acids 410 and 563) in the center of the protein.
# Function
During myotube differentiation, myopodin interacts with stress fibers prior to co-localizing with alpha actinin-2 at Z-discs in mature striated muscle cells. Myopodin has been shown to shuttle between the nucleus and cytoplasm in myoblasts and myotubes in response to stress; its export from the nucleus is sensitive to lemtomycin B. The nuclear localization of myopodin is sensitive to Importin 13, which directly binds myopodin and facilitates its translocation. Importin binding and nuclear import of myopodin appears to be mediated by serine/threonine phosphorylation-dependent binding of myopodin to 14-3-3 beta Myopodin appears to regulate compartmentalized, intracellular signal transduction between the Z-disc and nucleus in cardiac muscle cells, by forming a Z-disc signaling complex with alpha actinin-2, calcineurin, CaMKII, muscle-specific A-kinase anchoring protein, and myomegalin. Specifically, phosphorylation by protein kinase A or CaMKII, and dephosphorylation by calcineurin facilitates the binding or release, respectively, of 14-3-3-beta, and the corresponding nuclear or cytoplasmic localization, respectively, of myopodin.
# Interactions
Myopodin interacts with:
- 14-3-3 beta,
- Actin, alpha, cardiac muscle 1,
- Actinin, alpha 2,
- Calcineurin,
- CaMKII,
- Importin 13, and
- Protein kinase A. | SYNPO2
Myopodin protein, also called Synaptopodin-2 is a protein that in humans is encoded by the SYNPO2 gene.[1][2][3] Myopodin is expressed in cardiac, smooth muscle and skeletal muscle, and localizes to Z-disc structures.
# Structure
Myopodin is a 117.4 kDa protein composed of 1093 amino acids,[4] although four alternatively-spliced isoforms have been described.[5] Myopodin contains one PPXY motif, multiple PXXP motifs, and two potential nuclear localization sequences (one N-terminal and one C-terminal).[1] PPXY motifs have been shown to mediate interactions, and PXXP motifs represent potential sites of interaction for SH3 domain-containing proteins. Myopodin contains a novel actin binding site (between amino acids 410 and 563) in the center of the protein.[1]
# Function
During myotube differentiation, myopodin interacts with stress fibers prior to co-localizing with alpha actinin-2 at Z-discs in mature striated muscle cells.[1] Myopodin has been shown to shuttle between the nucleus and cytoplasm in myoblasts and myotubes in response to stress; its export from the nucleus is sensitive to lemtomycin B.[1] The nuclear localization of myopodin is sensitive to Importin 13, which directly binds myopodin and facilitates its translocation.[6] Importin binding and nuclear import of myopodin appears to be mediated by serine/threonine phosphorylation-dependent binding of myopodin to 14-3-3 beta [7] Myopodin appears to regulate compartmentalized, intracellular signal transduction between the Z-disc and nucleus in cardiac muscle cells, by forming a Z-disc signaling complex with alpha actinin-2, calcineurin, CaMKII, muscle-specific A-kinase anchoring protein, and myomegalin.[8] Specifically, phosphorylation by protein kinase A or CaMKII, and dephosphorylation by calcineurin facilitates the binding or release, respectively, of 14-3-3-beta, and the corresponding nuclear or cytoplasmic localization, respectively, of myopodin.[8]
# Interactions
Myopodin interacts with:
- 14-3-3 beta,[8]
- Actin, alpha, cardiac muscle 1,[1]
- Actinin, alpha 2,[1]
- Calcineurin,[8]
- CaMKII,[8]
- Importin 13,[6] and
- Protein kinase A.[8] | https://www.wikidoc.org/index.php/SYNPO2 | |
0a4a6fe2b9fe4fba56c098284d5c767c5a87470f | wikidoc | Saliva | Saliva
# Overview
Saliva is the watery and usually frothy substance produced in the mouths of humans and some animals. In animals, saliva is produced in and secreted from the salivary glands.
# Functions
## Digestion
The digestive functions of saliva include moistening food, and helping to create a food bolus, so it can be swallowed easily. Saliva contains the enzyme amylase that breaks some starches down into maltose and dextrin. Thus, digestion of food occurs within the mouth, even before food reaches the stomach. Salivary glands also secrete enzyme to start fat digestion. This is useful for infants to digest the fat in milk.
## Role in emesis
The importance of the salivary protective function can be demonstrated by considering a scenario where an individual is about to vomit. Vomit contains gastric substances which are extremely acidic and will erode teeth. A protective reflex occurs before the individual prepares to vomit. Signals are sent from the brain to the salivary glands via the involuntary nervous system to cause increased saliva secretion, even before vomiting occurs. Thus, when vomiting does occur, there is already saliva present in the mouth acting to minimize the acidity and thus prevent destruction of tooth structure.
## Pellicle deposits
In addition to this, saliva is responsible for depositing salivary pellicle that covers the entirety of the tooth surfaces. This pellicle is believed to play a role in plaque formation, though there is evidence that it may also act as a protective barrier between acids and the tooth surface.
## Disinfectants
A common belief is that saliva contained in the mouth has natural disinfectants, which leads people to believe it is beneficial to "lick their wounds". Researchers at the University of Florida at Gainesville have discovered a protein called nerve growth factor (NGF) in the saliva of mice. Wounds doused with NGF healed twice as fast as untreated and unlicked wounds; therefore, saliva does have some curative powers in some species. NGF has not been found in human saliva; however, researchers find human saliva contains such antibacterial agents as secretory IgA, lactoferrin, and lactoperoxidase. It has not been shown that human licking of wounds disinfects them, but licking is likely to help clean the wound by removing larger contaminants such as dirt and may help to directly remove infective bodies by brushing them away. Therefore, licking would be a way of washing, useful if purer water isn't available to the animal or person.
The mouth of animals is the habitat of many bacteria, some of which may be pathogenic. Animal (including human) bites are routinely treated with systemic antibiotics because of the risk of septicemia.
# Stimulation
The production of saliva is stimulated both by the sympathetic nervous system and the parasympathetic.
The saliva stimulated by sympathetic innervation is thicker, and saliva stimulated parasympathetically is more watery.
# Daily salivary output
There has been some disagreement regarding the daily salivary output in a healthy individual. Today, it is believed that the average person produces approximately 700mL of saliva per day, which is much less than was once thought.
# Contents
Produced in salivary glands, saliva is 98% water, but it contains many important substances, including electrolytes, mucus, antibacterial compounds and various enzymes.
It is a fluid containing:
- Water
- Electrolytes:
2-21 mmol/L sodium (lower than blood plasma)
10-36 mmol/L potassium (higher than plasma)
1.2-2.8 mmol/L calcium
0.08-0.5 mmol/L magnesium
5-40 mmol/L chloride (lower than plasma)
25 mmol/L bicarbonate (higher than plasma)
1.4-39 mmol/L phosphate
- 2-21 mmol/L sodium (lower than blood plasma)
- 10-36 mmol/L potassium (higher than plasma)
- 1.2-2.8 mmol/L calcium
- 0.08-0.5 mmol/L magnesium
- 5-40 mmol/L chloride (lower than plasma)
- 25 mmol/L bicarbonate (higher than plasma)
- 1.4-39 mmol/L phosphate
- Mucus. Mucus in saliva mainly consists of mucopolysaccharides and glycoproteins;
- Antibacterial compounds (thiocyanate, hydrogen peroxide, and secretory immunoglobulin A)
- Various enzymes. There are three major enzymes found in saliva.
α-amylase (EC3.2.1.1). Amylase starts the digestion of starch and lipase fat before the food is even swallowed. It has a pH optima of 7.4.
lysozyme (EC3.2.1.17). Lysozyme acts to lyse bacteria.
lingual lipase (EC3.1.1.3). Lingual lipase has a pH optimum ~4.0 so it is not activated till entering an acidic environment.
Minor enzymes include salivary acid phosphatases A+B (EC3.1.3.2), N-acetylmuramyl-L-alanine amidase (EC3.5.1.28), NAD(P)H dehydrogenase-quinone (EC1.6.99.2), salivary lactoperoxidase (EC1.11.1.7), superoxide dismutase (EC1.15.1.1), glutathione transferase (EC2.5.1.18), class 3 aldehyde dehydrogenase (EC1.2.1.3), glucose-6-phosphate isomerase (EC5.3.1.9), and tissue kallikrein (EC3.4.21.35).
- α-amylase (EC3.2.1.1). Amylase starts the digestion of starch and lipase fat before the food is even swallowed. It has a pH optima of 7.4.
- lysozyme (EC3.2.1.17). Lysozyme acts to lyse bacteria.
- lingual lipase (EC3.1.1.3). Lingual lipase has a pH optimum ~4.0 so it is not activated till entering an acidic environment.
- Minor enzymes include salivary acid phosphatases A+B (EC3.1.3.2), N-acetylmuramyl-L-alanine amidase (EC3.5.1.28), NAD(P)H dehydrogenase-quinone (EC1.6.99.2), salivary lactoperoxidase (EC1.11.1.7), superoxide dismutase (EC1.15.1.1), glutathione transferase (EC2.5.1.18), class 3 aldehyde dehydrogenase (EC1.2.1.3), glucose-6-phosphate isomerase (EC5.3.1.9), and tissue kallikrein (EC3.4.21.35).
- Cells: Possibly as much as 8 million human and 500 million bacterial cells per mL. The presence of bacterial products (small organic acids, amines, and thiols) causes saliva to sometimes exhibit foul odor.
- Opiorphin, a newly researched pain-killing substance found in human saliva. | Saliva
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Saliva is the watery and usually frothy substance produced in the mouths of humans and some animals. In animals, saliva is produced in and secreted from the salivary glands.
# Functions
## Digestion
The digestive functions of saliva include moistening food, and helping to create a food bolus, so it can be swallowed easily. Saliva contains the enzyme amylase that breaks some starches down into maltose and dextrin. Thus, digestion of food occurs within the mouth, even before food reaches the stomach. Salivary glands also secrete enzyme to start fat digestion. This is useful for infants to digest the fat in milk.
## Role in emesis
The importance of the salivary protective function can be demonstrated by considering a scenario where an individual is about to vomit. Vomit contains gastric substances which are extremely acidic and will erode teeth. A protective reflex occurs before the individual prepares to vomit. Signals are sent from the brain to the salivary glands via the involuntary nervous system to cause increased saliva secretion, even before vomiting occurs. Thus, when vomiting does occur, there is already saliva present in the mouth acting to minimize the acidity and thus prevent destruction of tooth structure.
## Pellicle deposits
In addition to this, saliva is responsible for depositing salivary pellicle that covers the entirety of the tooth surfaces. This pellicle is believed to play a role in plaque formation, though there is evidence that it may also act as a protective barrier between acids and the tooth surface.[1]
## Disinfectants
A common belief is that saliva contained in the mouth has natural disinfectants, which leads people to believe it is beneficial to "lick their wounds". Researchers at the University of Florida at Gainesville have discovered a protein called nerve growth factor (NGF) in the saliva of mice. Wounds doused with NGF healed twice as fast as untreated and unlicked wounds; therefore, saliva does have some curative powers in some species. NGF has not been found in human saliva; however, researchers find human saliva contains such antibacterial agents as secretory IgA, lactoferrin, and lactoperoxidase.[2] It has not been shown that human licking of wounds disinfects them, but licking is likely to help clean the wound by removing larger contaminants such as dirt and may help to directly remove infective bodies by brushing them away. Therefore, licking would be a way of washing, useful if purer water isn't available to the animal or person.
The mouth of animals is the habitat of many bacteria, some of which may be pathogenic. Animal (including human) bites are routinely treated with systemic antibiotics because of the risk of septicemia.
# Stimulation
The production of saliva is stimulated both by the sympathetic nervous system and the parasympathetic.[3]
The saliva stimulated by sympathetic innervation is thicker, and saliva stimulated parasympathetically is more watery.
# Daily salivary output
There has been some disagreement regarding the daily salivary output in a healthy individual. Today, it is believed that the average person produces approximately 700mL of saliva per day, which is much less than was once thought.
# Contents
Produced in salivary glands, saliva is 98% water, but it contains many important substances, including electrolytes, mucus, antibacterial compounds and various enzymes. [4]
It is a fluid containing:
- Water
- Electrolytes:
2-21 mmol/L sodium (lower than blood plasma)
10-36 mmol/L potassium (higher than plasma)
1.2-2.8 mmol/L calcium
0.08-0.5 mmol/L magnesium
5-40 mmol/L chloride (lower than plasma)
25 mmol/L bicarbonate (higher than plasma)
1.4-39 mmol/L phosphate
- 2-21 mmol/L sodium (lower than blood plasma)
- 10-36 mmol/L potassium (higher than plasma)
- 1.2-2.8 mmol/L calcium
- 0.08-0.5 mmol/L magnesium
- 5-40 mmol/L chloride (lower than plasma)
- 25 mmol/L bicarbonate (higher than plasma)
- 1.4-39 mmol/L phosphate
- Mucus. Mucus in saliva mainly consists of mucopolysaccharides and glycoproteins;
- Antibacterial compounds (thiocyanate, hydrogen peroxide, and secretory immunoglobulin A)
- Various enzymes. There are three major enzymes found in saliva.
α-amylase (EC3.2.1.1). Amylase starts the digestion of starch and lipase fat before the food is even swallowed. It has a pH optima of 7.4.
lysozyme (EC3.2.1.17). Lysozyme acts to lyse bacteria.
lingual lipase (EC3.1.1.3). Lingual lipase has a pH optimum ~4.0 so it is not activated till entering an acidic environment.
Minor enzymes include salivary acid phosphatases A+B (EC3.1.3.2), N-acetylmuramyl-L-alanine amidase (EC3.5.1.28), NAD(P)H dehydrogenase-quinone (EC1.6.99.2), salivary lactoperoxidase (EC1.11.1.7), superoxide dismutase (EC1.15.1.1), glutathione transferase (EC2.5.1.18), class 3 aldehyde dehydrogenase (EC1.2.1.3), glucose-6-phosphate isomerase (EC5.3.1.9), and tissue kallikrein (EC3.4.21.35).
- α-amylase (EC3.2.1.1). Amylase starts the digestion of starch and lipase fat before the food is even swallowed. It has a pH optima of 7.4.
- lysozyme (EC3.2.1.17). Lysozyme acts to lyse bacteria.
- lingual lipase (EC3.1.1.3). Lingual lipase has a pH optimum ~4.0 so it is not activated till entering an acidic environment.
- Minor enzymes include salivary acid phosphatases A+B (EC3.1.3.2), N-acetylmuramyl-L-alanine amidase (EC3.5.1.28), NAD(P)H dehydrogenase-quinone (EC1.6.99.2), salivary lactoperoxidase (EC1.11.1.7), superoxide dismutase (EC1.15.1.1), glutathione transferase (EC2.5.1.18), class 3 aldehyde dehydrogenase (EC1.2.1.3), glucose-6-phosphate isomerase (EC5.3.1.9), and tissue kallikrein (EC3.4.21.35).
- Cells: Possibly as much as 8 million human and 500 million bacterial cells per mL. The presence of bacterial products (small organic acids, amines, and thiols) causes saliva to sometimes exhibit foul odor.
- Opiorphin, a newly researched pain-killing substance found in human saliva. | https://www.wikidoc.org/index.php/Saccharidase | |
23c629a9dd8af0e795d6c54e0b53c770a7a6662d | wikidoc | Sacrum | Sacrum
# Overview
The sacrum is a large, triangular bone at the base of the spine and at the upper and back part of the pelvic cavity, where it is inserted like a wedge between the two hip bones. Its upper part connects with the last lumbar vertebra, and bottom part with the coccyx (tailbone).
It is curved upon itself and placed obliquely (that is, tilted forward). It is concave facing forwards, thus its curvature is considered a kyphosis. The base projects forward as the sacral promontory internally, and articulates with the last lumbar vertebra to form the prominent sacrovertebral angle. The central part is curved outward towards the posterior, allowing greater room for the pelvic cavity.
# Etymology
The name is derived from the Latin sacer, "sacred", a translation of the Greek hieron (osteon), meaning sacred or strong bone. This is supposedly derived from the belief that it could not be destroyed and was the part that would allow rising from the dead.
# Parts
- The pelvic surface of sacrum is concave from above downward, and slightly so from side to side.
- The dorsal surface of sacrum is convex and narrower than the pelvic.
- The lateral surface of sacrum is broad above, but narrowed into a thin edge below.
- The base of the sacrum, which is broad and expanded, is directed upward and forward.
- The apex (apex oss. sacri) is directed downward, and presents an oval facet for articulation with the coccyx.
- The vertebral canal (canalis sacralis; sacral canal) runs throughout the greater part of the bone; above, it is triangular in form; below, its posterior wall is incomplete, from the non-development of the laminae and spinous processes. It lodges the sacral nerves, and its walls are perforated by the anterior and posterior sacral foramina through which these nerves pass out.
# Articulations
The sacrum articulates with four bones:
- the last lumbar vertebra above
- the coccyx below
- the hip bone on either side
Although in most people the sacro-iliac joints are tightly bound and immobile, some are able to rotate the sacrum forward a few degrees vis-à-vis the ilia. This motion is sometimes called "nutation", and the reverse motion "counter-nutation."
It is called the sacrum when referred to all of the parts combined, but sacral vertebrae when referred individually.
# Sexual dimorphism
The sacrum is noticeably sexually dimorphic (differently-shaped in males and females).
In the female the sacrum is shorter and wider than in the male; the lower half forms a greater angle with the upper; the upper half is nearly straight, the lower half presenting the greatest amount of curvature. The bone is also directed more obliquely backward; this increases the size of the pelvic cavity and renders the sacrovertebral angle more prominent.
In the male the curvature is more evenly distributed over the whole length of the bone, and is altogether greater than in the female.
# Variations
The sacrum, in some cases, consists of six pieces ; occasionally the number is reduced to four . The bodies of the first and second vertebrae may fail to unite.
Sometimes the uppermost transverse tubercles are not joined to the rest of the ala on one or both sides, or the sacral canal may be open throughout a considerable part of its length, in consequence of the imperfect development of the laminae and spinous processes.
The sacrum, also, varies considerably with respect to its degree of curvature
# Additional images
- Vertebral column.
- Sacrum, dorsal surface.
- Lateral surfaces of sacrum and coccyx.
- Base of sacrum.
- Median sagittal section of the sacrum.
- Vertebral column.
- Left Levator ani from within.
- The posterior divisions of the sacral nerves.
- Median sagittal section of male pelvis.
- Median sagittal section of female pelvis. | Sacrum
Template:Infobox Bone
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
The sacrum is a large, triangular bone at the base of the spine and at the upper and back part of the pelvic cavity, where it is inserted like a wedge between the two hip bones. Its upper part connects with the last lumbar vertebra, and bottom part with the coccyx (tailbone).
It is curved upon itself and placed obliquely (that is, tilted forward). It is concave facing forwards, thus its curvature is considered a kyphosis. The base projects forward as the sacral promontory internally, and articulates with the last lumbar vertebra to form the prominent sacrovertebral angle. The central part is curved outward towards the posterior, allowing greater room for the pelvic cavity.
# Etymology
The name is derived from the Latin sacer, "sacred", a translation of the Greek hieron (osteon), meaning sacred or strong bone.[1] This is supposedly derived from the belief that it could not be destroyed and was the part that would allow rising from the dead.[2]
# Parts
- The pelvic surface of sacrum is concave from above downward, and slightly so from side to side.
- The dorsal surface of sacrum is convex and narrower than the pelvic.
- The lateral surface of sacrum is broad above, but narrowed into a thin edge below.
- The base of the sacrum, which is broad and expanded, is directed upward and forward.
- The apex (apex oss. sacri) is directed downward, and presents an oval facet for articulation with the coccyx.
- The vertebral canal (canalis sacralis; sacral canal) runs throughout the greater part of the bone; above, it is triangular in form; below, its posterior wall is incomplete, from the non-development of the laminae and spinous processes. It lodges the sacral nerves, and its walls are perforated by the anterior and posterior sacral foramina through which these nerves pass out.
# Articulations
The sacrum articulates with four bones:
- the last lumbar vertebra above
- the coccyx below
- the hip bone on either side
Although in most people the sacro-iliac joints are tightly bound and immobile, some are able to rotate the sacrum forward a few degrees vis-à-vis the ilia. This motion is sometimes called "nutation", and the reverse motion "counter-nutation."[3]
It is called the sacrum when referred to all of the parts combined, but sacral vertebrae when referred individually.
# Sexual dimorphism
The sacrum is noticeably sexually dimorphic (differently-shaped in males and females).
In the female the sacrum is shorter and wider than in the male; the lower half forms a greater angle with the upper; the upper half is nearly straight, the lower half presenting the greatest amount of curvature. The bone is also directed more obliquely backward; this increases the size of the pelvic cavity and renders the sacrovertebral angle more prominent.
In the male the curvature is more evenly distributed over the whole length of the bone, and is altogether greater than in the female.
# Variations
The sacrum, in some cases, consists of six pieces [2]; occasionally the number is reduced to four [3]. The bodies of the first and second vertebrae may fail to unite.
Sometimes the uppermost transverse tubercles are not joined to the rest of the ala on one or both sides, or the sacral canal may be open throughout a considerable part of its length, in consequence of the imperfect development of the laminae and spinous processes.
The sacrum, also, varies considerably with respect to its degree of curvature
# Additional images
- Vertebral column.
-
- Sacrum, dorsal surface.
- Lateral surfaces of sacrum and coccyx.
- Base of sacrum.
- Median sagittal section of the sacrum.
- Vertebral column.
- Left Levator ani from within.
- The posterior divisions of the sacral nerves.
- Median sagittal section of male pelvis.
- Median sagittal section of female pelvis. | https://www.wikidoc.org/index.php/Sacral | |
5da57b8f734a029112c886fede14840041122b2c | wikidoc | Sacsin | Sacsin
Sacsin also known as DnaJ homolog subfamily C member 29 (DNAJC29) is a protein that in humans is encoded by the SACS gene. Sacsin is a Hsp70 co-chaperone.
# Function
This gene consists of nine exons including a gigantic exon spanning more than 12.8k bp. It encodes the sacsin protein, which includes a UBQ region at the N-terminus, a HEPN domain at the C-terminus and a DnaJ region upstream of the HEPN domain. This modular protein is essential for normal mitochondrial network organization. The gene is highly expressed in the central nervous system, also found in skin, skeletal muscles and at low levels in the pancreas. Mutations in this gene result in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), a neurodegenerative disorder characterized by early-onset cerebellar ataxia with spasticity and peripheral neuropathy.
# Clinical significance
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a very rare neurodegenerative genetic disorder that results from mutations in the gene that produces Sacsin. Afflicted persons suffer from loss of balance, loss of muscle control and spasticity. | Sacsin
Sacsin also known as DnaJ homolog subfamily C member 29 (DNAJC29) is a protein that in humans is encoded by the SACS gene.[1][2] Sacsin is a Hsp70 co-chaperone.[3]
# Function
This gene consists of nine exons including a gigantic exon spanning more than 12.8k bp. It encodes the sacsin protein, which includes a UBQ region at the N-terminus, a HEPN domain at the C-terminus and a DnaJ region upstream of the HEPN domain. This modular protein is essential for normal mitochondrial network organization.[4] The gene is highly expressed in the central nervous system, also found in skin, skeletal muscles and at low levels in the pancreas. Mutations in this gene result in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), a neurodegenerative disorder characterized by early-onset cerebellar ataxia with spasticity and peripheral neuropathy.[2]
# Clinical significance
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a very rare neurodegenerative genetic disorder that results from mutations in the gene that produces Sacsin. Afflicted persons suffer from loss of balance, loss of muscle control and spasticity.[5] | https://www.wikidoc.org/index.php/Sacsin | |
14b26bc182333750e31af3b7320752938f5a367b | wikidoc | Sclera | Sclera
The sclera is the opaque (usually white), fibrous, protective layer of the eye containing collagen and elastic fibers. In children, it is thinner and shows some of the underlying pigment, appearing slightly blue. In the old, however, fatty deposits on the sclera can make it appear slightly yellow.
The sclera forms the posterior five sixths of the connective tissue coat of the globe. The sclera maintains the shape of the globe, offering resistance to internal and external forces, and provides an attachment for the extraocular muscle insertions. The thickness of the sclera varies from 1mm at the posterior pole to 0.3 mm just behind the rectus muscle insertions.
# Additional images
- Interior of anterior half of bulb of eye.
- The terminal portion of the optic nerve and its entrance into the eyeball, in horizontal section.
- The interior of the posterior half of the left eyeball. | Sclera
Template:Infobox Anatomy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
The sclera is the opaque (usually white), fibrous, protective layer of the eye containing collagen and elastic fibers.[1] In children, it is thinner and shows some of the underlying pigment, appearing slightly blue. In the old, however, fatty deposits on the sclera can make it appear slightly yellow.
The sclera forms the posterior five sixths of the connective tissue coat of the globe. The sclera maintains the shape of the globe, offering resistance to internal and external forces, and provides an attachment for the extraocular muscle insertions. The thickness of the sclera varies from 1mm at the posterior pole to 0.3 mm just behind the rectus muscle insertions.
# Additional images
- Interior of anterior half of bulb of eye.
- The terminal portion of the optic nerve and its entrance into the eyeball, in horizontal section.
- The interior of the posterior half of the left eyeball. | https://www.wikidoc.org/index.php/Sclera | |
c46946c6c77a9358c1a5a56447ada485ef334e29 | wikidoc | SeHCAT | SeHCAT
# Overview
SeHCAT is the usual name for 23-seleno-25-homo-tauro-cholic acid (selenium homocholic acid taurine or tauroselcholic acid). It is used in a clinical test to diagnose bile acid malabsorption.
# Development
SeHCAT is a taurine-conjugated bile acid analog which was synthesized for use as a radiopharmaceutical to investigate in vivo the enterohepatic circulation of bile salts. By incorporating the gamma-emitter 75Se into the SeHCAT molecule, the retention in the body or the loss of this compound into the feces could be studied easily using a standard gamma camera, available in most clinical nuclear medicine departments.
SeHCAT has been shown to be absorbed from the gut and excreted into the bile at the same rate as cholic acid, one of the major natural bile acids in humans. It undergoes secretion into the biliary tree, gallbladder and intestine in response to food, and is reabsorbed efficiently in the ileum, with kinetics similar to natural bile acids. It was soon shown to be the most convenient and accurate method available to assess and measure bile acid turnover in the intestine. SeHCAT testing was commercially developed by Amersham International Ltd (Amersham plc is now part of GE Healthcare Medical Diagnostics division) for clinical use to investigate malabsorption in patients with diarrhea. This test has replaced 14C-labeled glycocholic acid (or taurocholic acid) breath tests and fecal bile acid measurements, which now have no place in the routine clinical investigation of malabsorption.
# Procedure
A capsule containing radiolabelled 75SeHCAT (with 370kBq of Selenium-75 and less than 0.1 mg SeHCAT) is taken orally. The physical half life of 75Se is approximately 118 days; activity is adjusted to a standard reference date.
Patients are often fasted before taking the capsule and swallow water to ensure passage of the capsule into the gastrointestinal tract. The effective dose of radiation for an adult given 370kBq of SeHCAT is 0.26mSv. (For comparison, the radiation exposure from an abdominal CT scan is quoted at 5.3mSv and annual background exposure in the UK 1-3mSv.) Measurements were originally performed with a whole body counter but are usually performed now with an uncollimated gamma camera. The patient is scanned supine or prone with anterior and posterior acquisition from head to thigh 1 to 3 hours after taking the capsule. Scanning is repeated after 7 days. Background values are subtracted and care must be taken to avoid external sources of radiation in a nuclear medicine department.
From these measurements, the percent retention of SeHCAT at 7 days is calculated. A 7-day SeHCAT retention value greater than 15% is considered to be normal, with values less than 15% signifing excessive bile acid loss, as found in bile acid malabsorption.
With more frequent measurements, it is possible to calculate SeHCAT retention whole body half-life; this is not routinely measured in a clinical setting. A half-life of greater than 2.8 days has been quoted as normal.
# Clinical use
The SeHCAT test is used to investigate patients with suspected bile acid malabsorption, who usually experience chronic diarrhea, often passing watery feces 5 to 10 times each day. When ileum has been removed following surgery, or is inflamed in Crohn's disease, the 7-day SeHCAT retention usually is abnormal, and most of these patients will benefit from treatment with bile acid sequestrants. The enterohepatic circulation of bile acids is reduced in these patients with ileal abnormalities and, as the normal bile acid retention exceeds 95%, only a small degree of change is needed. Bile acid malabsorption can also be secondary to cholecystectomy, vagotomy and other disorders affecting intestinal motility or digestion such as radiation enteritis, celiac disease and small intestinal bacterial overgrowth.
A similar picture of chronic diarrhea, an abnormal SeHCAT retention and a response to bile acid sequestrants, in the absence of other disorders of the intestine, is characteristic of idiopathic bile acid malabsorption – also called primary bile acid diarrhea. These patients are frequently misdiagnosed as having the irritable bowel syndrome, as clinicians fail to recognize the condition, do not think of performing a SeHCAT test, or do not have it available.
There have been at least 18 studies of the use of SeHCAT testing in diarrhea-predominant irritable bowel syndrome patients. When these data were combined, 32% of 1223 patients had a SeHCAT 7-day retention of less than 10%, and 80% of these reported a response to cholestyramine, a bile acid sequestrant. | SeHCAT
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
SeHCAT is the usual name for 23-seleno-25-homo-tauro-cholic acid (selenium homocholic acid taurine or tauroselcholic acid).[1] It is used in a clinical test to diagnose bile acid malabsorption.
# Development
SeHCAT is a taurine-conjugated bile acid analog which was synthesized for use as a radiopharmaceutical to investigate in vivo the enterohepatic circulation of bile salts.[2] By incorporating the gamma-emitter 75Se into the SeHCAT molecule, the retention in the body or the loss of this compound into the feces could be studied easily using a standard gamma camera, available in most clinical nuclear medicine departments.
SeHCAT has been shown to be absorbed from the gut and excreted into the bile at the same rate as cholic acid, one of the major natural bile acids in humans. It undergoes secretion into the biliary tree, gallbladder and intestine in response to food, and is reabsorbed efficiently in the ileum, with kinetics similar to natural bile acids.[2][3] It was soon shown to be the most convenient and accurate method available to assess and measure bile acid turnover in the intestine.[4] SeHCAT testing was commercially developed by Amersham International Ltd (Amersham plc is now part of GE Healthcare Medical Diagnostics division) for clinical use to investigate malabsorption in patients with diarrhea. This test has replaced 14C-labeled glycocholic acid (or taurocholic acid) breath tests and fecal bile acid measurements, which now have no place in the routine clinical investigation of malabsorption.
# Procedure
A capsule containing radiolabelled 75SeHCAT (with 370kBq of Selenium-75 and less than 0.1 mg SeHCAT) is taken orally. The physical half life of 75Se is approximately 118 days; activity is adjusted to a standard reference date.
Patients are often fasted before taking the capsule and swallow water to ensure passage of the capsule into the gastrointestinal tract. The effective dose of radiation for an adult given 370kBq of SeHCAT is 0.26mSv.[5] (For comparison, the radiation exposure from an abdominal CT scan is quoted at 5.3mSv and annual background exposure in the UK 1-3mSv.[6]) Measurements were originally performed with a whole body counter but are usually performed now with an uncollimated gamma camera. The patient is scanned supine or prone with anterior and posterior acquisition from head to thigh 1 to 3 hours after taking the capsule. Scanning is repeated after 7 days. Background values are subtracted and care must be taken to avoid external sources of radiation in a nuclear medicine department.
From these measurements, the percent retention of SeHCAT at 7 days is calculated. A 7-day SeHCAT retention value greater than 15% is considered to be normal, with values less than 15% signifing excessive bile acid loss, as found in bile acid malabsorption.
With more frequent measurements, it is possible to calculate SeHCAT retention whole body half-life; this is not routinely measured in a clinical setting. A half-life of greater than 2.8 days has been quoted as normal.[7]
# Clinical use
The SeHCAT test is used to investigate patients with suspected bile acid malabsorption, who usually experience chronic diarrhea, often passing watery feces 5 to 10 times each day. When ileum has been removed following surgery, or is inflamed in Crohn's disease, the 7-day SeHCAT retention usually is abnormal, and most of these patients will benefit from treatment with bile acid sequestrants.[8][9] The enterohepatic circulation of bile acids is reduced in these patients with ileal abnormalities and, as the normal bile acid retention exceeds 95%, only a small degree of change is needed. Bile acid malabsorption can also be secondary to cholecystectomy, vagotomy and other disorders affecting intestinal motility or digestion such as radiation enteritis, celiac disease and small intestinal bacterial overgrowth.
A similar picture of chronic diarrhea, an abnormal SeHCAT retention and a response to bile acid sequestrants, in the absence of other disorders of the intestine, is characteristic of idiopathic bile acid malabsorption – also called primary bile acid diarrhea. These patients are frequently misdiagnosed as having the irritable bowel syndrome, as clinicians fail to recognize the condition, do not think of performing a SeHCAT test, or do not have it available.[10]
There have been at least 18 studies of the use of SeHCAT testing in diarrhea-predominant irritable bowel syndrome patients. When these data were combined, 32% of 1223 patients had a SeHCAT 7-day retention of less than 10%, and 80% of these reported a response to cholestyramine, a bile acid sequestrant.[11] | https://www.wikidoc.org/index.php/SeHCAT | |
9f0fa3f6b44829cf5f3aaa1dbfac623a2f328f95 | wikidoc | Sponge | Sponge
# Overview
The sponges or poriferans (from Latin porus "pore" and ferre "to bear") are animals of the phylum Porifera. Porifera translates to "Pore-bearer". They are primitive, sessile, mostly marine, water dwelling, filter feeders that pump water through their bodies to filter out particles of food matter. Sponges represent the simplest of animals. With no true tissues (parazoa), they lack muscles, nerves, and internal organs. Their similarity to colonial choanoflagellates shows the probable evolutionary jump from unicellular to multicellular organisms. There are over 5,000 modern species of sponges known, and they can be found attached to surfaces anywhere from the intertidal zone to as deep as 8,500 m (29,000 feet) or further. Though the fossil record of sponges dates back to the Neoproterozoic Era, new species are still commonly discovered.
# Anatomy and morphology
Sponges have several cell types:
- Choanocytes (also known as "collar cells") function as the sponge's digestive system, and are remarkably similar to the protistan choanoflagellates. The collars are composed of microvilli and are used to filter particles out of the water. The beating of the choanocytes’ flagella creates the sponge’s water current.
- Porocytes are tubular cells that make up the pores into the sponge body through the mesohyl.
- Pinacocytes which form the pinacoderm, the outer epidermal layer of cells. This is the closest approach to true tissue in sponges
- Myocytes are modified pinacocytes which control the size of the osculum and pore openings and thus the water flow.
- Archaeocytes (or amoebocytes) have many functions; they are totipotent cells which can transform into sclerocytes, spongocytes, or collencytes. They also have a role in nutrient transport and sexual reproduction.
- Sclerocytes secrete calcareous siliceous spicules which reside in the mesohyl.
- Spongocytes secrete spongin, collagen-like fibers which make up the mesohyl.
- Collencytes secrete collagen.
- Spicules are stiffened rods or spikes made of calcium carbonate or silica which are used for structure and defense.
- Cells are arranged in a gelatinous non-cellular matrix called mesohyl.
Sponges have three body types: asconoid, syconoid, and leuconoid.
Asconoid sponges are tubular with a central shaft called the spongocoel. The beating of choanocyte flagella forces water into the spongocoel through pores in the body wall. Choanocytes line the spongocoel and filter nutrients out of the water.
Syconoid sponges are similar to asconoids. They have a tubular body with a single osculum, but the body wall is thicker and more complex than that of asconoids and contains choanocyte-lined radial canals that empty into the spongocoel. Water enters through a large number of dermal ostia into incurrent canals and then filters through tiny openings called prosopyles into the radial canals. There food is ingested by the choanocytes. Syconoids do not usually form highly branched colonies as asconoids do. During their development, syconoid sponges pass through an asconoid stage.
Leuconoid sponges lack a spongocoel and instead have flagellated chambers, containing choanocytes, which are led to and out of via canals.
# Physiology
Sponges have no true circulatory system; instead, they create a water current which is used for circulation. Dissolved gases are brought to cells and enter the cells via simple diffusion. Metabolic wastes are also transferred to the water through diffusion. Sponges pump remarkable amounts of water. Leuconia, for example, is a small leuconoid sponge about 10 cm tall and 1 cm in diameter. It is estimated that water enters through more than 80,000 incurrent canals at a speed of 6cm per minute. However, because Leuconia has more than 2 million flagellated chambers whose combined diameter is much greater than that of the canals, water flow through chambers slows to 3.6cm per hour. Such a flow rate allows easy food capture by the collar cells. All water is expelled through a single osculum at a velocity of about 8.5 cm/second: a jet force capable of carrying waste products some distance away from the sponge.
Sponges have no respiratory or excretory organs; both functions occur by diffusion in individual cells. Contractile vacuoles are found in archaeocytes and choanocytes of freshwater sponges. The only visible activities and responses in sponges, other than propulsion of water, are slight alterations in shape and closing and opening of incurrent and excurrent pores, and these movements are slow.
# Taxonomy
Sponges are classified as animals, despite the fact that they lack gastrulated embryos, extracellular digestive cavities, nerves, muscles, tissues, and obvious sensory structures, which all other animals possess. At one time, sponges were considered plants, as they appear to share the plant-like characteristic of being rooted to a single spot, although some species of sponge are motile. Unlike almost all plants, sponges do not photosynthesize, and they lack cellulose cell walls, which are common to all plants.
Long thought to be the most archaic branch of the animals, sponges are considered as useful models of the earliest multicellular ancestors of animals; although there is no evidence that they actually are, or that they are even descended from early animals. Sponge choanocytes (feeding cells) are likely to be an homologous cell type to choanoflagellates - a group of unicellular and colonial protists that are believed to be the immediate precursors of animals. Sponges appear to be, at best, a divergent side-group from the main animal line.
It has been suggested that the sponges are paraphyletic to the other animals. Otherwise they are sometimes treated as their own subkingdom, the Parazoa. Similar fossil animals known as Chancelloria are no longer regarded as sponges.
One phylogenetic hypothesis based on molecular analysis proposes that the phylum Porifera is itself paraphyletic, and should be split into two new phyla, the Calcarea and the Silicarea.
Sponges are divided into classes based on the type of spicules in their skeleton. The three classes of sponges are bony (Calcarea), glass (Hexactenellida), and spongin (Demospongiae). Some taxonomists have suggested a fourth class, Sclerospongiae, of coralline sponges, but the modern consensus is that coralline sponges have arisen several times and are not closely related. In addition to these four, a fifth and extinct class has been proposed: Archaeocyatha. While these ancient animals have been phylogenetically vague for years, the current general consensus is that they were a type of sponge.
Although 90% of modern sponges are demosponges, fossilized remains of this type are less common than those of other types because their skeletons are composed of relatively soft spongin that does not fossilize well. The fossil Archaeocyantha may also belong here, though their skeletons are solid rather than separated into spicules.
# Geological history
The fossil record of sponges is not abundant, except in a few scattered localities. Some fossil sponges have worldwide distribution, while others are restricted to certain areas. Sponge fossils such as Hydnoceras and Prismodictya are found in the Devonian rocks of New York state. In Europe the Jurassic limestone of the Swabian Alps are composed largely of sponge remains, some of which are well preserved. Many sponges are found in the Cretaceous Lower Greensand and Chalk Formations of England, and in rocks from the upper part of the Cretaceous period in France. A famous locality for fossil sponges is the Cretaceous Faringdon Sponge Gravels in Faringdon, Oxfordshire in England. An older sponge is the Cambrian Vauxia. Sponges have long been important agents of bioerosion in shells and carbonate rocks. Their borings extend back to the Ordovician in the fossil record.
Fossil sponges differ in size from 1 cm (0.4 inches) to more than 1 meter (3.3 feet). They vary greatly in shape, being commonly vase-shapes (such as Ventriculites), spherical (such as Porosphaera), saucer-shaped (such as Astraeospongia), pear-shaped (such as Siphonia), leaf-shaped (such as Elasmostoma), branching (such as Doryderma), irregular or encrusting.
Detailed identification of many fossil sponges relies on the study of thin sections.
# Ecology and Reproduction
Modern sponges are predominantly marine, with some 150 species adapted to freshwater environments. Their habitats range from the inter-tidal zone to depths of 6,000 metres (19,680 feet). Certain types of sponges are limited in the range of depths at which they are found. Sponges are worldwide in their distribution, and range from waters of the polar regions to the tropical regions. Sponges are most abundant in both numbers of individuals and species in warmer waters.
Adult sponges are largely sessile, and live in an attached position. However, it has been noted that certain sponges can move slowly by directing their water current in a certain direction with myocytes. The greatest numbers of sponges are usually to be found where a firm means of fastening is provided, such as on a rocky ocean bottom. Some kinds of sponges are able to attach themselves to soft sediment by means of a root-like base. Sponges also live in quiet clear waters, because if the sediment is agitated by wave action or by currents, it tends to block the pores of the animal, lessening its ability to feed and survive.
Recent evidence suggests that a new disease called Aplysina red band syndrome (ARBS) is threatening sponges in the Caribbean. Aplysina red band syndrome causes Aplysina to develop one or more rust-coloured leading edges to their structure, sometimes with a surrounding area of necrotic tissue so that the lesion causes a contiguous band around some or all of the sponge's branch.
## Reproduction
Sponges can reproduce sexually or asexually.
Asexual reproduction is through internal and external budding. External budding occurs when the parent sponge grows a bud on the outside of its body. This will either break away or stay connected. Internal budding occurs when archaeocytes collect in the mesohyl and become surrounded by spongin. The internal bud is called a gemmule. An asexually reproduced sponge has exactly the same genetic material as the parent.
In sexual reproduction, sperm are dispersed by water currents and enter neighbouring sponges. All sponges of a particular species release their sperm at approximately the same time. Fertilization occurs internally, in the mesohyl. Flagellated zygotes develop and then leave the parent sponge to settle somewhere else.
Although sponges are hermaphroditic (both male and female), they are not self-fertile. Most sponges are sequential hermaphrodites, capable of producing eggs or sperm, but not both at the same time.
# Use
## By dolphins
In 1997, use of sponges as a tool was described in Bottlenose Dolphins in Shark Bay. A dolphin will attach a marine sponge to its rostrum, which is presumably then used to protect it when searching for food in the sandy sea bottom. The behaviour, known as sponging, has only been observed in this bay, and is almost exclusively shown by females. This is the only known case of tool use in marine mammals outside of Sea Otters. An elaborate study in 2005 showed that mothers most likely teach the behaviour to their daughters.
## By humans
### Skeleton as absorbent
In common usage, the term sponge is applied to the skeleton of the animal, from which the tissue has been removed by maceration and washing, leaving just the spongin scaffolding. Calcareous and siliceous sponges are too harsh for similar use. Commercial sponges are derived from various species and come in many grades, from fine soft "lamb's wool" sponges to the coarse grades used for washing cars.
The manufacture of rubber-, plastic- and cellulose-based synthetic sponges has significantly reduced the commercial sponge fishing industry in recent years.
The luffa "sponge", also spelled "loofah," commonly sold for use in the kitchen or the shower, is not derived from an animal sponge, but from the locules of a gourd (Cucurbitaceae).
### Antibiotic compounds
Sponges have medicinal potential due to the presence of antimicrobial compounds in either the sponge itself or their microbial symbionts.
# Bibliography
- C. Hickman Jr., L. Roberts and A Larson (2003). Animal Diversity (3rd ed.). New York: McGraw-Hill. ISBN 0-07-234903-4..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- New disease threatens sponges, Practical Fishkeeping | Sponge
# Overview
The sponges or poriferans (from Latin porus "pore" and ferre "to bear") are animals of the phylum Porifera. Porifera translates to "Pore-bearer". They are primitive, sessile, mostly marine, water dwelling, filter feeders that pump water through their bodies to filter out particles of food matter. Sponges represent the simplest of animals. With no true tissues (parazoa), they lack muscles, nerves, and internal organs. Their similarity to colonial choanoflagellates shows the probable evolutionary jump from unicellular to multicellular organisms. There are over 5,000 modern species of sponges known, and they can be found attached to surfaces anywhere from the intertidal zone to as deep as 8,500 m (29,000 feet) or further. Though the fossil record of sponges dates back to the Neoproterozoic Era, new species are still commonly discovered.
# Anatomy and morphology
Sponges have several cell types:
- Choanocytes (also known as "collar cells") function as the sponge's digestive system, and are remarkably similar to the protistan choanoflagellates. The collars are composed of microvilli and are used to filter particles out of the water. The beating of the choanocytes’ flagella creates the sponge’s water current.
- Porocytes are tubular cells that make up the pores into the sponge body through the mesohyl.
- Pinacocytes which form the pinacoderm, the outer epidermal layer of cells. This is the closest approach to true tissue in sponges
- Myocytes are modified pinacocytes which control the size of the osculum and pore openings and thus the water flow.
- Archaeocytes (or amoebocytes) have many functions; they are totipotent cells which can transform into sclerocytes, spongocytes, or collencytes. They also have a role in nutrient transport and sexual reproduction.
- Sclerocytes secrete calcareous siliceous spicules which reside in the mesohyl.
- Spongocytes secrete spongin, collagen-like fibers which make up the mesohyl.
- Collencytes secrete collagen.
- Spicules are stiffened rods or spikes made of calcium carbonate or silica which are used for structure and defense.
- Cells are arranged in a gelatinous non-cellular matrix called mesohyl.
Sponges have three body types: asconoid, syconoid, and leuconoid.
Asconoid sponges are tubular with a central shaft called the spongocoel. The beating of choanocyte flagella forces water into the spongocoel through pores in the body wall. Choanocytes line the spongocoel and filter nutrients out of the water.
Syconoid sponges are similar to asconoids. They have a tubular body with a single osculum, but the body wall is thicker and more complex than that of asconoids and contains choanocyte-lined radial canals that empty into the spongocoel. Water enters through a large number of dermal ostia into incurrent canals and then filters through tiny openings called prosopyles into the radial canals. There food is ingested by the choanocytes. Syconoids do not usually form highly branched colonies as asconoids do. During their development, syconoid sponges pass through an asconoid stage.
Leuconoid sponges lack a spongocoel and instead have flagellated chambers, containing choanocytes, which are led to and out of via canals.
# Physiology
Sponges have no true circulatory system; instead, they create a water current which is used for circulation. Dissolved gases are brought to cells and enter the cells via simple diffusion. Metabolic wastes are also transferred to the water through diffusion. Sponges pump remarkable amounts of water. Leuconia, for example, is a small leuconoid sponge about 10 cm tall and 1 cm in diameter. It is estimated that water enters through more than 80,000 incurrent canals at a speed of 6cm per minute. However, because Leuconia has more than 2 million flagellated chambers whose combined diameter is much greater than that of the canals, water flow through chambers slows to 3.6cm per hour.[1] Such a flow rate allows easy food capture by the collar cells. All water is expelled through a single osculum at a velocity of about 8.5 cm/second: a jet force capable of carrying waste products some distance away from the sponge.
Sponges have no respiratory or excretory organs; both functions occur by diffusion in individual cells. Contractile vacuoles are found in archaeocytes and choanocytes of freshwater sponges. The only visible activities and responses in sponges, other than propulsion of water, are slight alterations in shape and closing and opening of incurrent and excurrent pores, and these movements are slow.
# Taxonomy
Sponges are classified as animals, despite the fact that they lack gastrulated embryos, extracellular digestive cavities, nerves, muscles, tissues, and obvious sensory structures, which all other animals possess. At one time, sponges were considered plants, as they appear to share the plant-like characteristic of being rooted to a single spot, although some species of sponge are motile. Unlike almost all plants, sponges do not photosynthesize, and they lack cellulose cell walls, which are common to all plants.
Long thought to be the most archaic branch of the animals, sponges are considered as useful models of the earliest multicellular ancestors of animals; although there is no evidence that they actually are, or that they are even descended from early animals. Sponge choanocytes (feeding cells) are likely to be an homologous cell type to choanoflagellates - a group of unicellular and colonial protists that are believed to be the immediate precursors of animals. Sponges appear to be, at best, a divergent side-group from the main animal line.
It has been suggested that the sponges are paraphyletic to the other animals. Otherwise they are sometimes treated as their own subkingdom, the Parazoa. Similar fossil animals known as Chancelloria are no longer regarded as sponges.
One phylogenetic hypothesis based on molecular analysis proposes that the phylum Porifera is itself paraphyletic, and should be split into two new phyla, the Calcarea and the Silicarea.
Sponges are divided into classes based on the type of spicules in their skeleton. The three classes of sponges are bony (Calcarea), glass (Hexactenellida), and spongin (Demospongiae). Some taxonomists have suggested a fourth class, Sclerospongiae, of coralline sponges, but the modern consensus is that coralline sponges have arisen several times and are not closely related.[2] In addition to these four, a fifth and extinct class has been proposed: Archaeocyatha. While these ancient animals have been phylogenetically vague for years, the current general consensus is that they were a type of sponge.
Although 90% of modern sponges are demosponges, fossilized remains of this type are less common than those of other types because their skeletons are composed of relatively soft spongin that does not fossilize well. The fossil Archaeocyantha may also belong here, though their skeletons are solid rather than separated into spicules.
# Geological history
The fossil record of sponges is not abundant, except in a few scattered localities. Some fossil sponges have worldwide distribution, while others are restricted to certain areas. Sponge fossils such as Hydnoceras and Prismodictya are found in the Devonian rocks of New York state. In Europe the Jurassic limestone of the Swabian Alps are composed largely of sponge remains, some of which are well preserved. Many sponges are found in the Cretaceous Lower Greensand and Chalk Formations of England, and in rocks from the upper part of the Cretaceous period in France. A famous locality for fossil sponges is the Cretaceous Faringdon Sponge Gravels in Faringdon, Oxfordshire in England. An older sponge is the Cambrian Vauxia. Sponges have long been important agents of bioerosion in shells and carbonate rocks. Their borings extend back to the Ordovician in the fossil record.
Fossil sponges differ in size from 1 cm (0.4 inches) to more than 1 meter (3.3 feet). They vary greatly in shape, being commonly vase-shapes (such as Ventriculites), spherical (such as Porosphaera), saucer-shaped (such as Astraeospongia), pear-shaped (such as Siphonia), leaf-shaped (such as Elasmostoma), branching (such as Doryderma), irregular or encrusting.
Detailed identification of many fossil sponges relies on the study of thin sections.
# Ecology and Reproduction
Modern sponges are predominantly marine, with some 150 species adapted to freshwater environments. Their habitats range from the inter-tidal zone to depths of 6,000 metres (19,680 feet). Certain types of sponges are limited in the range of depths at which they are found. Sponges are worldwide in their distribution, and range from waters of the polar regions to the tropical regions. Sponges are most abundant in both numbers of individuals and species in warmer waters.
Adult sponges are largely sessile, and live in an attached position. However, it has been noted that certain sponges can move slowly by directing their water current in a certain direction with myocytes. The greatest numbers of sponges are usually to be found where a firm means of fastening is provided, such as on a rocky ocean bottom. Some kinds of sponges are able to attach themselves to soft sediment by means of a root-like base. Sponges also live in quiet clear waters, because if the sediment is agitated by wave action or by currents, it tends to block the pores of the animal, lessening its ability to feed and survive.
Recent evidence suggests that a new disease called Aplysina red band syndrome (ARBS) is threatening sponges in the Caribbean.[1] Aplysina red band syndrome causes Aplysina to develop one or more rust-coloured leading edges to their structure, sometimes with a surrounding area of necrotic tissue so that the lesion causes a contiguous band around some or all of the sponge's branch.
## Reproduction
Sponges can reproduce sexually or asexually.
Asexual reproduction is through internal and external budding. External budding occurs when the parent sponge grows a bud on the outside of its body. This will either break away or stay connected. Internal budding occurs when archaeocytes collect in the mesohyl and become surrounded by spongin. The internal bud is called a gemmule. An asexually reproduced sponge has exactly the same genetic material as the parent.
In sexual reproduction, sperm are dispersed by water currents and enter neighbouring sponges. All sponges of a particular species release their sperm at approximately the same time.[citation needed] Fertilization occurs internally, in the mesohyl. Flagellated zygotes develop and then leave the parent sponge to settle somewhere else.
Although sponges are hermaphroditic (both male and female), they are not self-fertile. Most sponges are sequential hermaphrodites, capable of producing eggs or sperm, but not both at the same time.
# Use
## By dolphins
In 1997, use of sponges as a tool was described in Bottlenose Dolphins in Shark Bay. A dolphin will attach a marine sponge to its rostrum, which is presumably then used to protect it when searching for food in the sandy sea bottom.[3] The behaviour, known as sponging, has only been observed in this bay, and is almost exclusively shown by females. This is the only known case of tool use in marine mammals outside of Sea Otters. An elaborate study in 2005 showed that mothers most likely teach the behaviour to their daughters.[4]
## By humans
### Skeleton as absorbent
In common usage, the term sponge is applied to the skeleton of the animal, from which the tissue has been removed by maceration and washing, leaving just the spongin scaffolding. Calcareous and siliceous sponges are too harsh for similar use. Commercial sponges are derived from various species and come in many grades, from fine soft "lamb's wool" sponges to the coarse grades used for washing cars.
The manufacture of rubber-, plastic- and cellulose-based synthetic sponges has significantly reduced the commercial sponge fishing industry in recent years.
The luffa "sponge", also spelled "loofah," commonly sold for use in the kitchen or the shower, is not derived from an animal sponge, but from the locules of a gourd (Cucurbitaceae).
### Antibiotic compounds
Sponges have medicinal potential due to the presence of antimicrobial compounds in either the sponge itself or their microbial symbionts.[5]
# Bibliography
Template:Sourcesstart
- C. Hickman Jr., L. Roberts and A Larson (2003). Animal Diversity (3rd ed.). New York: McGraw-Hill. ISBN 0-07-234903-4..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- New disease threatens sponges, Practical Fishkeeping
Template:Sourcesend | https://www.wikidoc.org/index.php/Sea_sponge | |
c66e5696adccdb8165c230af824d242d4381c022 | wikidoc | Senile | Senile
# Overview
Senile means related to aging. For example, senile weakness is a form of weakness happening in old people.
The word senile comes from the latin sen meaning "old". This word was first coined in 1661. In Persian language, "سن" (pronounced as "sen") means "age".
Senile may also refer to Dementia, which is a disease typically seen in the elderly. | Senile
For patient information, click here
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Senile means related to aging. For example, senile weakness is a form of weakness happening in old people.[1]
The word senile comes from the latin sen meaning "old". This word was first coined in 1661.[1] In Persian language, "سن" (pronounced as "sen") means "age".
Senile may also refer to Dementia, which is a disease typically seen in the elderly. | https://www.wikidoc.org/index.php/Senile | |
6f7fe7322fb5afc69e0e199523fda83163fcbc7f | wikidoc | Sensor | Sensor
A sensor is a device which measures a physical quantity and converts it into a signal which can be read by an observer or by an instrument. For example, a mercury thermometer converts the measured temperature into expansion and contraction of a liquid which can be read on a calibrated glass tube. A thermocouple converts temperature to an output voltage which can be read by a voltmeter. For accuracy, all sensors need to be calibrated against known standards.
Sensors are used in everyday objects such as touch-sensitive elevator buttons and lamps which dim or brighten by touching the base. There are also innumerable applications for sensors of which most people are never aware. Applications include automobiles, machines, aerospace, medicine, industry, and robotics.
A sensor's sensitivity indicates how much the sensor's output changes when the measured quantity changes. For instance, if the mercury in a thermometer moves 1cm when the temperature changes by 1°, the sensitivity is 1cm/1°. Sensors that measure very small changes must have very high sensitivities.
Technological progress allows more and more sensors to be manufactured on a microscopic scale as microsensors using MEMS technology. In most cases, a microsensor reaches a significantly higher speed and sensitivity compared with macroscopic approaches. See also MEMS sensor generations.
# Types
Because sensors are a type of transducer, they change one form of energy into another. For this reason, sensors can be classified according to the type of energy transfer that they detect.
## Thermal
- temperature sensors: thermometers, thermocouples, temperature sensitive resistors (thermistors and resistance temperature detectors), bi-metal thermometers and thermostats
- heat sensors: bolometer, calorimeter, heat flux sensor
## Electromagnetic
- electrical resistance sensors: ohmmeter, multimeter
- electrical current sensors: galvanometer, ammeter
- electrical voltage sensors: leaf electroscope, voltmeter
- electrical power sensors: watt-hour meters
- magnetism sensors: magnetic compass, fluxgate compass, magnetometer, Hall effect device
- metal detectors
- RADAR
## Mechanical
- pressure sensors: altimeter, barometer, barograph, pressure gauge, air speed indicator, rate-of-climb indicator, variometer
- gas and liquid flow sensors: flow sensor, anemometer, flow meter, gas meter, water meter, mass flow sensor
- gas and liquid viscosity and density: viscometer, hydrometer, oscillating U-tube
- mechanical sensors: acceleration sensor, position sensor, selsyn, switch, strain gauge
- humidity sensors: hygrometer
## Chemical
- Chemical proportion sensors: oxygen sensors, ion-selective electrodes, pH glass electrodes, redox electrodes, and carbon monoxide detectors.
- Odour sensors: Tin-oxide gas sensors, and Quartz Microbalance sensors.
## Optical radiation
- light time-of-flight. Used in modern surveying equipment, a short pulse of light is emitted and returned by a retroreflector. The return time of the pulse is proportional to the distance and is related to atmospheric density in a predictable way - see LIDAR.
- light sensors, or photodetectors, including semiconductor devices such as photocells, photodiodes, phototransistors, CCDs, and Image sensors; vacuum tube devices like photo-electric tubes, photomultiplier tubes; and mechanical instruments such as the Nichols radiometer.
- infra-red sensor, especially used as occupancy sensor for lighting and environmental controls.
- proximity sensor- A type of distance sensor but less sophisticated. Only detects a specific proximity. May be optical - combination of a photocell and LED or laser. Applications in cell phones, paper detector in photocopiers, auto power standby/shutdown mode in notebooks and other devices. May employ a magnet and a Hall effect device.
- scanning laser- A narrow beam of laser light is scanned over the scene by a mirror. A photocell sensor located at an offset responds when the beam is reflected from an object to the sensor, whence the distance is calculated by triangulation.
- focus. A large aperture lens may be focused by a servo system. The distance to an in-focus scene element may be determined by the lens setting.
- binocular. Two images gathered on a known baseline are brought into coincidence by a system of mirrors and prisms. The adjustment is used to determine distance. Used in some cameras (called range-finder cameras) and on a larger scale in early battleship range-finders
- interferometry. Interference fringes between transmitted and reflected lightwaves produced by a coherent source such as a laser are counted and the distance is calculated. Capable of extremely high precision.
- scintillometers measure atmospheric optical disturbances.
- fiber optic sensors.
- short path optical interception - detection device consists of a light-emitting diode illuminating a phototransistor, with the end position of a mechanical device detected by a moving flag intercepting the optical path, useful for determining an initial position for mechanisms driven by stepper motors.
## Ionising radiation
- radiation sensors: Geiger counter, dosimeter, Scintillation counter, Neutron detection
- subatomic particle sensors: Particle detector, scintillator, Wire chamber, cloud chamber, bubble chamber. See Category:Particle detectors
## Acoustic
- acoustic : uses ultrasound time-of-flight echo return. Used in mid 20th century polaroid cameras and applied also to robotics. Even older systems like Fathometers (and fish finders) and other 'Tactical Active' Sonar (Sound Navigation And Ranging) systems in naval applications which mostly use audible sound frequencies.
- sound sensors : microphones, hydrophones, seismometers.
## Other types
- motion sensors: radar gun, speedometer, tachometer, odometer, occupancy sensor, turn coordinator
- orientation sensors: gyroscope, artificial horizon, ring laser gyroscope
- distance sensor (noncontacting) Several technologies can be applied to sense distance: magnetostriction
### Non Initialized systems
- Gray code strip or wheel- a number of photodetectors can sense a pattern, creating a binary number. The gray code is a mutated pattern that ensures that only one bit of information changes with each measured step, thus avoiding ambiguities.
### Initialized systems
These require starting from a known distance and accumulate incremental changes in measurements.
- Quadrature wheel- A disk-shaped optical mask is driven by a gear train. Two photocells detecting light passing through the mask can determine a partial revolution of the mask and the direction of that rotation.
- whisker sensor- A type of touch sensor and proximity sensor.
# Classification of measurement errors
A good sensor obeys the following rules:
- the sensor should be sensitive to the measured property
- the sensor should be insensitive to any other property
- the sensor should not influence the measured property
Ideal sensors are designed to be linear. The output signal of such a sensor is linearly proportional to the value of the measured property. The sensitivity is then defined as the ratio between output signal and measured property. For example, if a sensor measures temperature and has a voltage output, the sensitivity is a constant with the unit ; this sensor is linear because the ratio is constant at all points of measurement.
If the sensor is not ideal, several types of deviations can be observed:
- The sensitivity may in practice differ from the value specified. This is called a sensitivity error, but the sensor is still linear.
- Since the range of the output signal is always limited, the output signal will eventually reach a minimum or maximum when the measured property exceeds the limits. The full scale range defines the maximum and minimum values of the measured property.
- If the output signal is not zero when the measured property is zero, the sensor has an offset or bias. This is defined as the output of the sensor at zero input.
- If the sensitivity is not constant over the range of the sensor, this is called nonlinearity. Usually this is defined by the amount the output differs from ideal behavior over the full range of the sensor, often noted as a percentage of the full range.
- If the deviation is caused by a rapid change of the measured property over time, there is a dynamic error. Often, this behaviour is described with a bode plot showing sensitivity error and phase shift as function of the frequency of a periodic input signal.
- If the output signal slowly changes independent of the measured property, this is defined as drift.
- Long term drift usually indicates a slow degradation of sensor properties over a long period of time.
- Noise is a random deviation of the signal that varies in time.
- Hysteresis is an error caused by when the measured property reverses direction, but there is some finite lag in time for the sensor to respond, creating a different offset error in one direction than in the other.
- If the sensor has a digital output, the output is essentially an approximation of the measured property. The approximation error is also called digitization error.
- If the signal is monitored digitally, limitation of the sampling frequency also can cause a dynamic error.
- The sensor may to some extent be sensitive to properties other than the property being measured. For example, most sensors are influenced by the temperature of their environment.
All these deviations can be classified as systematic errors or random errors.
Systematic errors can sometimes be compensated for by means of some kind of calibration strategy.
Noise is a random error that can be reduced by signal processing, such as filtering, usually at the expense of the dynamic behaviour of the sensor.
## Resolution
The resolution of a sensor is the smallest change it can detect in the quantity that it is measuring. Often in a digital display, the least significant digit will fluctuate, indicating that changes of that magnitude are only just resolved. The resolution is related to the precision with which the measurement is made.
For example, a scanning probe (a fine tip near a surface collects an electron tunnelling current) can resolve atoms and molecules.
# Biological sensors
All living organisms contain biological sensors with functions similar to those of the mechanical devices described. Most of these are specialized cells that are sensitive to:
- light, motion, temperature, magnetic fields, gravity, humidity, vibration, pressure, electrical fields, sound, and other physical aspects of the external environment;
- physical aspects of the internal environment, such as stretch, motion of the organism, and position of appendages (proprioception);
- an enormous array of environmental molecules, including toxins, nutrients, and pheromones;
- estimation of biomolecules interaction and some kinetics parameters;
- many aspects of the internal metabolic milieu, such as glucose level, oxygen level, or osmolality;
- an equally varied range of internal signal molecules, such as hormones, neurotransmitters, and cytokines;
- and even the differences between proteins of the organism itself and of the environment or alien creatures.
Artificial sensors that mimic biological sensors by using a biological sensitive component, are called biosensors.
The human senses are examples of specialized neuronal sensors. See Sense.
# Geodetic sensors
Geodetic measuring devices measure georeferenced displacements or movements in one, two or three dimensions. It includes the use of instruments such as total stations, levels and global navigation satellite system receivers. | Sensor
A sensor is a device which measures a physical quantity and converts it into a signal which can be read by an observer or by an instrument. For example, a mercury thermometer converts the measured temperature into expansion and contraction of a liquid which can be read on a calibrated glass tube. A thermocouple converts temperature to an output voltage which can be read by a voltmeter. For accuracy, all sensors need to be calibrated against known standards.
Sensors are used in everyday objects such as touch-sensitive elevator buttons and lamps which dim or brighten by touching the base. There are also innumerable applications for sensors of which most people are never aware. Applications include automobiles, machines, aerospace, medicine, industry, and robotics.
A sensor's sensitivity indicates how much the sensor's output changes when the measured quantity changes. For instance, if the mercury in a thermometer moves 1cm when the temperature changes by 1°, the sensitivity is 1cm/1°. Sensors that measure very small changes must have very high sensitivities.
Technological progress allows more and more sensors to be manufactured on a microscopic scale as microsensors using MEMS technology. In most cases, a microsensor reaches a significantly higher speed and sensitivity compared with macroscopic approaches. See also MEMS sensor generations.
# Types
Because sensors are a type of transducer, they change one form of energy into another. For this reason, sensors can be classified according to the type of energy transfer that they detect.
## Thermal
- temperature sensors: thermometers, thermocouples, temperature sensitive resistors (thermistors and resistance temperature detectors), bi-metal thermometers and thermostats
- heat sensors: bolometer, calorimeter, heat flux sensor
## Electromagnetic
- electrical resistance sensors: ohmmeter, multimeter
- electrical current sensors: galvanometer, ammeter
- electrical voltage sensors: leaf electroscope, voltmeter
- electrical power sensors: watt-hour meters
- magnetism sensors: magnetic compass, fluxgate compass, magnetometer, Hall effect device
- metal detectors
- RADAR
## Mechanical
- pressure sensors: altimeter, barometer, barograph, pressure gauge, air speed indicator, rate-of-climb indicator, variometer
- gas and liquid flow sensors: flow sensor, anemometer, flow meter, gas meter, water meter, mass flow sensor
- gas and liquid viscosity and density: viscometer, hydrometer, oscillating U-tube
- mechanical sensors: acceleration sensor, position sensor, selsyn, switch, strain gauge
- humidity sensors: hygrometer
## Chemical
- Chemical proportion sensors: oxygen sensors, ion-selective electrodes, pH glass electrodes, redox electrodes, and carbon monoxide detectors.
- Odour sensors: Tin-oxide gas sensors, and Quartz Microbalance sensors.
## Optical radiation
- light time-of-flight. Used in modern surveying equipment, a short pulse of light is emitted and returned by a retroreflector. The return time of the pulse is proportional to the distance and is related to atmospheric density in a predictable way - see LIDAR.
- light sensors, or photodetectors, including semiconductor devices such as photocells, photodiodes, phototransistors, CCDs, and Image sensors; vacuum tube devices like photo-electric tubes, photomultiplier tubes; and mechanical instruments such as the Nichols radiometer.
- infra-red sensor, especially used as occupancy sensor for lighting and environmental controls.
- proximity sensor- A type of distance sensor but less sophisticated. Only detects a specific proximity. May be optical - combination of a photocell and LED or laser. Applications in cell phones, paper detector in photocopiers, auto power standby/shutdown mode in notebooks and other devices. May employ a magnet and a Hall effect device.
- scanning laser- A narrow beam of laser light is scanned over the scene by a mirror. A photocell sensor located at an offset responds when the beam is reflected from an object to the sensor, whence the distance is calculated by triangulation.
- focus. A large aperture lens may be focused by a servo system. The distance to an in-focus scene element may be determined by the lens setting.
- binocular. Two images gathered on a known baseline are brought into coincidence by a system of mirrors and prisms. The adjustment is used to determine distance. Used in some cameras (called range-finder cameras) and on a larger scale in early battleship range-finders
- interferometry. Interference fringes between transmitted and reflected lightwaves produced by a coherent source such as a laser are counted and the distance is calculated. Capable of extremely high precision.
- scintillometers measure atmospheric optical disturbances.
- fiber optic sensors.
- short path optical interception - detection device consists of a light-emitting diode illuminating a phototransistor, with the end position of a mechanical device detected by a moving flag intercepting the optical path, useful for determining an initial position for mechanisms driven by stepper motors.
## Ionising radiation
- radiation sensors: Geiger counter, dosimeter, Scintillation counter, Neutron detection
- subatomic particle sensors: Particle detector, scintillator, Wire chamber, cloud chamber, bubble chamber. See Category:Particle detectors
## Acoustic
- acoustic : uses ultrasound time-of-flight echo return. Used in mid 20th century polaroid cameras and applied also to robotics. Even older systems like Fathometers (and fish finders) and other 'Tactical Active' Sonar (Sound Navigation And Ranging) systems in naval applications which mostly use audible sound frequencies.
- sound sensors : microphones, hydrophones, seismometers.
## Other types
- motion sensors: radar gun, speedometer, tachometer, odometer, occupancy sensor, turn coordinator
- orientation sensors: gyroscope, artificial horizon, ring laser gyroscope
- distance sensor (noncontacting) Several technologies can be applied to sense distance: magnetostriction
### Non Initialized systems
- Gray code strip or wheel- a number of photodetectors can sense a pattern, creating a binary number. The gray code is a mutated pattern that ensures that only one bit of information changes with each measured step, thus avoiding ambiguities.
### Initialized systems
These require starting from a known distance and accumulate incremental changes in measurements.
- Quadrature wheel- A disk-shaped optical mask is driven by a gear train. Two photocells detecting light passing through the mask can determine a partial revolution of the mask and the direction of that rotation.
- whisker sensor- A type of touch sensor and proximity sensor.
# Classification of measurement errors
A good sensor obeys the following rules:
- the sensor should be sensitive to the measured property
- the sensor should be insensitive to any other property
- the sensor should not influence the measured property
Ideal sensors are designed to be linear. The output signal of such a sensor is linearly proportional to the value of the measured property. The sensitivity is then defined as the ratio between output signal and measured property. For example, if a sensor measures temperature and has a voltage output, the sensitivity is a constant with the unit [V/K]; this sensor is linear because the ratio is constant at all points of measurement.
If the sensor is not ideal, several types of deviations can be observed:
- The sensitivity may in practice differ from the value specified. This is called a sensitivity error, but the sensor is still linear.
- Since the range of the output signal is always limited, the output signal will eventually reach a minimum or maximum when the measured property exceeds the limits. The full scale range defines the maximum and minimum values of the measured property.
- If the output signal is not zero when the measured property is zero, the sensor has an offset or bias. This is defined as the output of the sensor at zero input.
- If the sensitivity is not constant over the range of the sensor, this is called nonlinearity. Usually this is defined by the amount the output differs from ideal behavior over the full range of the sensor, often noted as a percentage of the full range.
- If the deviation is caused by a rapid change of the measured property over time, there is a dynamic error. Often, this behaviour is described with a bode plot showing sensitivity error and phase shift as function of the frequency of a periodic input signal.
- If the output signal slowly changes independent of the measured property, this is defined as drift.
- Long term drift usually indicates a slow degradation of sensor properties over a long period of time.
- Noise is a random deviation of the signal that varies in time.
- Hysteresis is an error caused by when the measured property reverses direction, but there is some finite lag in time for the sensor to respond, creating a different offset error in one direction than in the other.
- If the sensor has a digital output, the output is essentially an approximation of the measured property. The approximation error is also called digitization error.
- If the signal is monitored digitally, limitation of the sampling frequency also can cause a dynamic error.
- The sensor may to some extent be sensitive to properties other than the property being measured. For example, most sensors are influenced by the temperature of their environment.
All these deviations can be classified as systematic errors or random errors.
Systematic errors can sometimes be compensated for by means of some kind of calibration strategy.
Noise is a random error that can be reduced by signal processing, such as filtering, usually at the expense of the dynamic behaviour of the sensor.
## Resolution
The resolution of a sensor is the smallest change it can detect in the quantity that it is measuring. Often in a digital display, the least significant digit will fluctuate, indicating that changes of that magnitude are only just resolved. The resolution is related to the precision with which the measurement is made.
For example, a scanning probe (a fine tip near a surface collects an electron tunnelling current) can resolve atoms and molecules.
# Biological sensors
All living organisms contain biological sensors with functions similar to those of the mechanical devices described. Most of these are specialized cells that are sensitive to:
- light, motion, temperature, magnetic fields, gravity, humidity, vibration, pressure, electrical fields, sound, and other physical aspects of the external environment;
- physical aspects of the internal environment, such as stretch, motion of the organism, and position of appendages (proprioception);
- an enormous array of environmental molecules, including toxins, nutrients, and pheromones;
- estimation of biomolecules interaction and some kinetics parameters;
- many aspects of the internal metabolic milieu, such as glucose level, oxygen level, or osmolality;
- an equally varied range of internal signal molecules, such as hormones, neurotransmitters, and cytokines;
- and even the differences between proteins of the organism itself and of the environment or alien creatures.
Artificial sensors that mimic biological sensors by using a biological sensitive component, are called biosensors.
The human senses are examples of specialized neuronal sensors. See Sense.
# Geodetic sensors
Geodetic measuring devices measure georeferenced displacements or movements in one, two or three dimensions. It includes the use of instruments such as total stations, levels and global navigation satellite system receivers. | https://www.wikidoc.org/index.php/Sensor | |
e8c4c6fbfe485f1c8b45b264026c439b2b3c1bcb | wikidoc | Serpin | Serpin
Serpins are a group of proteins with similar structures that were first identified as a set of proteins able to inhibit proteases. The name serpin is derived from this activity - serine protease inhibitors.
The first members of the serpin superfamily to be extensively studied were the human plasma proteins antithrombin and antitrypsin, which play key roles in controlling blood coagulation and inflammation, respectively. Initially, research focused upon their role in human disease: antithrombin deficiency results in thrombosis and antitrypsin deficiency causes emphysema. In 1980 Hunt and Dayhoff made the surprising discovery that both these molecules share significant amino acid sequence similarity to the major protein in chicken egg white, ovalbumin, and they proposed a new protein superfamily. Over 1000 serpins have now been identified, these include 36 human proteins, as well as molecules in plants, bacteria, archaea and certain viruses. Serpins are thus the largest and most diverse family of protease inhibitors.
While most serpins control proteolytic cascades, certain serpins do not inhibit enzymes, but instead perform diverse functions such as storage (ovalbumin, in egg white), hormone carriage proteins (thyroxine-binding globulin, cortisol binding globulin) and tumor suppressor genes (maspin). The term serpin is used to describe these latter members as well, despite their noninhibitory function.
As serpins control processes such as coagulation and inflammation, these proteins are the target of medical research. However, serpins are also of particular interest to the structural biology and protein folding communities, because they undergo a unique and dramatic change in shape (or conformational change) when they inhibit target proteases. This is unusual - most classical protease inhibitors function as simple "lock and key" molecules that bind to and block access to the protease active site (see for example, bovine pancreatic trypsin inhibitor). While the serpin mechanism of protease inhibition confers certain advantages, it also has drawbacks and serpins are vulnerable to mutations that result in protein misfolding and the formation of inactive long chain polymers (serpinopathies). Serpin polymerisation reduces the amount of active inhibitor, as well as accumulation of serpin polymers causing cell death and organ failure. For example, the serpin antitrypsin is primarily produced in the liver, and antitrypsin polymerisation causes liver cirrhosis. Understanding serpinopathies also provides insights on protein misfolding in general, a process common to many human diseases, such as Alzheimer’s and CJD.
# Proteases inhibited by serpins
Most inhibitory serpins target chymotrypsin-like serine proteases (see Table 1). These enzymes are defined by the presence of a nucleophilic serine residue in their catalytic site. Examples include thrombin, trypsin and human neutrophil elastase.
Some serpins inhibit other classes of protease and are termed "cross class inhibitors". For example squamous cell carcinoma antigen 1 (SCCA-1) and the avian serpin myeloid and erythroid nuclear termination stage specific protein (MENT) both inhibit papain-like cysteine proteases
The viral serpin crmA is a suppressor of the inflammatory response through inhibition of IL-1 and IL-18 processing by the cysteine protease caspase-1. Cysteine proteases differ from serine proteases in that they are defined by the presence of a nucleophilic cysteine residue, rather than a serine residue, in their catalytic site. Nonetheless, the enzymatic chemistry is similar, and serpins most likely inhibit both classes of enzyme in a similar fashion.
# Localisation and general biological roles
Approximately two thirds of human serpins perform extracellular roles. For example, extracellular serpins regulate the proteolytic cascades central to blood clotting (antithrombin), the inflammatory response (antitrypsin, antichymotrypsin and C1 inhibitor) and tissue remodelling (PAI-1). Non-inhibitory extracellular serpins also perform important roles. Thyroxine-binding globulin and cortisol binding globulin transport the sterol hormones thyroxine and cortisol respectively. The protease renin cleaves off a ten amino acid N-terminal peptide from angiotensinogen to produce the peptide hormone angiotensin I. Table 1 at the bottom of this article provides a brief summary of human serpin function as well as some of the diseases that result from serpin deficiency.
The first Intracellular members of the serpin superfamily were identified in the early 1990s. As all nine serpins in Caenorhabditis elegans lack signal sequences, they are probably intracellular. Based upon these data it seems likely that the ancestral serpin to human serpins was an intracellular molecule.
The protease targets of intracellular inhibitory serpins have been more difficult to identify. Characterisation is complicated by these molecules appearing to perform overlapping roles, as well as the lack of precise functional equivalents of human serpins in model organisms such as the mouse. An important function of intracellular serpins may be to protect against the inappropriate activity of proteases inside the cell. For example, one of the best characterised human intracellular serpins is SERPINB9, which inhibits the cytotoxic granule protease granzyme B. In doing so, SERPINB9 may protect against inadvertent release of granzyme B and premature or unwanted activation of cell death pathways.
Intracellular serpins also perform roles distinct from protease inhibition. For example, maspin, a non-inhibitory serpin, is important for preventing metastasis in breast and prostate cancers. Another example is the avian nuclear cysteine protease inhibitor MENT, which acts as a chromatin remodelling molecule in avian red blood cells.
Phylogenetic studies show that most intracellular serpins belong to a single clade (see table 1). Exceptions include the non-inhibitory heat shock serpin HSP47, which is a chaperone essential for proper folding of collagen and cycles between the cis-Golgi and the endoplasmic reticulum.
# Structure
Structural biology has played a central role in the understanding of serpin function and biology. Over eighty serpin structures, in a variety of different conformations (described below) have been determined to date. Although the function of serpins varies widely, these molecules all share a common structure (or fold).
The structure of the non-inhibitory serpin ovalbumin, and the inhibitory serpin antitrypsin revealed the archetype native serpin fold. All typically have three β-sheets (termed A, B and C) and eight or nine α-helices (hA-hI) (see figure 1). Serpins also possess an exposed region termed the reactive centre loop (RCL) that in inhibitory molecules includes the specificity determining region and forms the initial interaction with the target protease. In antitrypsin, the RCL is held at the top of the molecule and is not pre-inserted into the A β-sheet (figure 1, left panel). This conformation commonly exists in dynamic equilibrium with a partially inserted native conformation seen in other inhibitory serpins (see figure 1, right panel).
# Conformational change and inhibitory mechanism
Early studies on serpins revealed that the mechanism by which these molecules inhibit target proteases appeared distinct from the lock-and-key-type mechanism utilised by small protease inhibitors such as the Kunitz-type inhibitors (eg. Basic pancreatic protease inhibitor). Indeed, serpins form covalent complexes with target proteases. Structural studies on serpins also revealed that inhibitory members of the family undergo an unusual conformational change, termed the Stressed to Relaxed (S to R) transition. During this structural transition the RCL inserts into β-sheet A (in red in figure 1 and 2) and forms an extra (fourth) β-strand. The serpin conformational change is key to the mechanism of inhibition of target proteases.
When attacking a substrate, serine proteases catalyze peptide bond cleavage in a two-step process. Initially, the catalytic serine performs a nucleophilic attack on the peptide bond of the substrate (Figure 3). This releases the new N-terminus and forms an ester-bond between the enzyme and the substrate. This covalent enzyme-substrate complex is called an acyl enzyme intermediate. Subsequently, this ester bond is hydrolysed and the new C-terminus is released. The RCL of a serpin acts as a substrate for its cognate protease. However, after the RCL is cleaved, but prior to hydrolysis of the acyl-enzyme intermediate, the serpin rapidly undergoes the S to R transition. Since the RCL is still covalently attached to the protease via the ester bond, the S to R transition causes the protease to be moved from the top to the bottom of the serpin. At the same time, the protease is distorted into a conformation where the acyl enzyme intermediate is hydrolysed extremely slowly. The protease thus remains covalently attached to the target protease and is thereby inhibited. Further, since the serpin has to be cleaved to inhibit the target protases, inhibition consumes the serpin as well. Serpins are therefore irreversible enzyme inhibitors. The serpin mechanism of inhibition is illustrated in figure 2 and several movies illustrating the serpin mechanism can be seen at this link.
# Conformational modulation of serpin activity
The conformational mobility of serpins provides a key advantage over static lock and key protease inhibitors. In particular, the function of inhibitory serpins can be readily controlled by specific cofactors. The X-ray crystal structures of antithrombin, heparin co-factor II, MENT and murine antichymotrypsin reveal that these serpins adopt a conformation where the first two amino acids of the RCL are inserted into the top of the A β-sheet (see figures 1 and 4). The partially inserted conformation is important because co-factors are able to conformationally switch partially inserted serpins into a fully expelled form. This conformational rearrangement makes the serpin a more effective inhibitor.
The archetypal example of this situation is antithrombin, which circulates in plasma in a partially inserted relatively inactive state. The primary specificity determining residue (the P1 Arginine) points towards the body of the serpin and is unavailable to the protease (Figure 4). Upon binding a high affinity heparin pentasaccharide sequence within long chain heparin, antithrombin undergoes a conformational change, RCL expulsion and exposure of the P1 Arginine. The heparin pentasaccharide bound form of antithrombin is thus a more effective inhibitor of thrombin and factor Xa (figure 4). Furthermore, both of these coagulation proteases contain binding sites (called exosites) for heparin. Heparin therefore also acts as a template for binding of both protease and serpin, further dramatically accelerating the interaction between the two parties (Figure 4). After the initial interaction, the final serpin complex is formed and the heparin moiety is released. This interaction is physiologically important. For example, after injury to the blood vessel wall heparin is exposed, and antithrombin is thus activated to control the clotting response. The understanding of the molecular basis of this interaction formed the basis of the development of Fondaparinux, a synthetic form of Heparin pentasaccharide used as an anti-clotting drug.
Certain serpins spontaneously undergo the S to R transition as part of their function, to form a conformation termed the latent state (Figure 5). In latent serpins the first strand of the C-sheet has to peel off to allow full RCL insertion. Latent serpins are unable to interact with proteases and are not protease inhibitors. The transition to latency represents a control mechanism for the serpin PAI-1. PAI-1 is released in the inhibitory conformation, however, undergoes conformational change to the latent state unless it is bound to the cofactor vitronectin. Thus PAI-1 contains an "auto-inactivation" mechanism. Similarly, antithrombin can also spontaneously convert to the latent state as part of its normal function. Finally, the N-terminus of tengpin, a serpin from Thermoanaerobacter tengcongensis, is required to lock the molecule in the native inhibitory state. Disruption of interactions made by the N-terminal region results in spontaneous conformational change of this serpin to the latent conformation.
# Serpin receptor interactions
In humans, extracellular serpin-enzyme complexes are rapidly cleared from circulation. One mechanism by which this occurs is the low density lipoprotein receptor related protein (LRP receptor), which binds to inhibitory complexes made by antithrombin, PA1-1 and neuroserpin, causing uptake and subsequent signalling events. Thus, as a consequence of the conformational change during serpin-enzyme complex formation, serpins may act as signalling molecules that alert cells to the presence of protease activity. The fate of intracellular serpin-enzyme complexes remains to be characterised.
# Conformational change and non-inhibitory function
Certain non-inhibitory serpins also use the serpin conformational change as part of their function. For example the native (S) form of thyroxine-binding globulin has high affinity for thyroxine, whereas the cleaved (R) form has low affinity. Similarly, native (S) Cortisol Binding Globulin (CBG) has higher affinity for cortisol than its cleaved (R) counterpart. Thus, in these serpins, RCL cleavage and the S to R transition has been commandeered to allow for ligand release, rather than protease inhibition.
# Serpins, serpinopathies and human disease
The complexity of the serpin mechanism renders these molecules vulnerable to inactivating mutations that promote inappropriate conformational change (or misfolding) and diseases ("serpinopathies"). Well characterised serpinopathies include emphysema, cirrhosis, thrombosis and dementia. Serpins thus belong to a large group of molecules such as the prion proteins and the glutamine repeat containing proteins that are susceptible to misfolding, causing conformational disease.
The ability to map the mutations in serpins that cause serpinopathies onto a structural framework aided understanding of the mechanism of normal serpin conformational changes, as well as serpin dysfunction. In particular, many serpin mutations that cause disease localise to two distinct regions of the molecule (highlighted in figure 1a) termed the shutter and the breach. The shutter and the breach contain highly-conserved residues and underlie the path of RCL insertion.
Serpin misfolding results in two common outcomes, both of which stem from the instability of the native (S) conformation. Firstly, pathogenic mutations in serpins can promote inappropriate transition to the monmoeric latent state. This causes disease because it reduces the amount of active inhibitory serpin. For example, the disease-linked antithrombin variants wibble and wobble, both promote formation of the latent state.
Secondly, and more insidiously, mutations in serpins may cause polymerisation. While the X-ray crystal structure of an intact serpin polymer remains to be determined, much biochemical, biophysical and structural data suggest that serpins "domain swap" with one another and form long-chain polymers. This may occur by a RCL of one serpin inserting into the A-sheet of another serpin, to form a chain, rather than inserting into its "own" A-sheet (see figure 6a for a model). The polymeric form is inactive and causes pathology. Serpin polymerisation causes disease in two ways. Firstly, the lack of active serpin results in uncontrolled protease activity and tissue destruction, this is seen in the case of antitrypsin deficiency. Secondly, the polymers themselves clog up the endoplasmic reticulum of cells that synthesize serpins, eventually resulting in cell death and tissue damage. In the case of antitrypsin deficiency, antitrypsin polymers cause the death of liver cells, eventually resulting in liver damage and cirrhosis.
Finally, it is worth highlighting a structure of a disease-linked human antichymotrypsin variant that demonstrates the extraordinary flexibility of the serpin scaffold. The structure of antichymotrypsin (Leucine 55 to Proline) revealed a novel "delta" conformation that may represent an intermediate between the native and latent state (Figure 6b). In the delta conformation four residues of the RCL are inserted into the top of β-sheet A. The bottom half of the sheet is filled as a result of one of the α-helices (the F-helix) partially switching to a strand-like conformation, completing the β-sheet hydrogen bonding. It is unclear whether other serpins can adopt this conformer, or whether this conformation has a functional role. However, this conformation may be important for thyroxine release by Thyroxine binding globulin.
# Other mechanisns of serpin-related disease
In humans, simple deficiency of many serpins (e.g. through a null mutation) may result in disease (see table 1).
Rarely, single amino acid changes in the RCL of a serpin alters the specificity of the inhibitor and allow it to target the wrong protease. For example, the Antitrypsin-Pittsburgh mutation (methionine 358 to arginine) allowed the serpin to inhibit thrombin, thus causing a bleeding disorder.
Serpins are suicide inhibitors, the RCL acting as a "bait". Certain disease-linked mutations in the RCL of human serpins permit true substrate-like behaviour and cleavage without complex formation. Such variants are speculated to affect the rate or the extent of RCL insertion into the A-sheet. These mutations effectively result in serpin deficiency through a failure to properly control the target protease.
Several non-inhibitory serpins play key roles in important human diseases. Most notably, maspin functions as a tumour suppressor in breast and prostate cancer. The mechanism of maspin function remains to be fully understood. Murine knockouts of maspin are lethal; these data suggest that maspin plays a key role in development.
# Evolution
Serpins were initially believed to be restricted to eukaryote organisms, but have since been found in a number of bacteria and archaea. It remains unclear whether these prokaryote genes are the descendants of an ancestral prokaryotic serpin or whether they are the product of lateral gene transfer (genetic transfer between organisms not by evolutionary descent). Rawlings et al., showed that serpins are the most widely distributed and largest family of protease inhibitors.
# Types of serpins
## Human serpins
The human genome encodes 36 serpins (see Law et al., (2006) for a recent review.). Table 1 lists each human serpin, together with brief notes in regards to each molecules function and the consequence (where known) of dysfunction or deficiency.
### Table 1
## Insect Serpins
Studies on Drosophila serpins reveal that Serpin-27A inhibits the Easter protease (the final protease in the Nudel, Gastrulation Defective, Snake and Easter proteolytic cascade) and thus controls dorsoventral patterning. Easter functions to cleave Spätzle (a chemokine-type ligand), which results in toll mediated signaling. In addition to its central role in embryonic patterning, toll signalling is also important for the innate immune response in insects. Accordingly, serpin-27A additionally functions to control the insect immune response.
## Worm Serpins
The genome of the nematode worm C. elegans contains nine serpins, however, only five of these molecules appear to function as protease inhibitors. One of these serpins, SRP-6, has been shown to perform a protective function and guard against stress induced calpain-associated lysosomal disruption. Further SRP-6 functions to inhibit lysosomal cysteine proteases released after lysosomal rupture. Accordingly, worms lacking SRP-6 are sensitive to stress. Most notably, SRP-6 knockout worms die when placed in water (the hypo-osmotic stress lethal phenotype or Osl). Based on these data it is suggested that lysosomes play a general and controllable role in determining cell fate.
## Plant serpins
The presence of serpins in plants has long been recognised - indeed, barley Z serpin is the major protein component in beer. The genome sequence of Arabidopsis thaliana is predicted to encode 29 serpins. Plant serpins are able to inhibit serine proteases in vitro. However, the absence of close relatives of chymotrypsin-like proteases in plants suggests that these molecules may instead perform an alternative function. Indeed, Arabidopsis serpin1 inhibits metacaspase-like proteases in vivo and may control cell death pathways.
## Prokaryote serpins
Predicted serpin genes are sporadicly distributed in prokaryotes. In vitro studies on some of these moelcules have revealed that they are able to inhibit proteases and it is suggested that they function as inhibitors in vivo. Interestingly, several prokaryote serpins are found in extremeophiles. Accordingly, and in contrast to mammalian serpins, these molecule possess elevated resistance to heat denaturation. The precise role of most bacterial serpins remains obscure, however, Clostridium thermocellum serpin localises to the cellulosome, a large extracellular mulitprotein complex that breaks down cellulose. It is suggested that the role of cellulosome-associated serpins may be to prevent unwanted protease activity against the cellulosome.
## Classification
In 2001, a serpin nomenclature was established. The naming system is based upon a phylogenetic analysis of ~500 serpins. This work classified the serpins into sixteen major clades, with several orphan sequences. The serpin family continues to grow - to date over 1000 serpins have been identified. | Serpin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [14]
Serpins are a group of proteins with similar structures that were first identified as a set of proteins able to inhibit proteases. The name serpin is derived from this activity - serine protease inhibitors.[2]
The first members of the serpin superfamily to be extensively studied were the human plasma proteins antithrombin and antitrypsin, which play key roles in controlling blood coagulation and inflammation, respectively. Initially, research focused upon their role in human disease: antithrombin deficiency results in thrombosis and antitrypsin deficiency causes emphysema. In 1980 Hunt and Dayhoff made the surprising discovery that both these molecules share significant amino acid sequence similarity to the major protein in chicken egg white, ovalbumin, and they proposed a new protein superfamily.[3] Over 1000 serpins have now been identified, these include 36 human proteins, as well as molecules in plants, bacteria, archaea and certain viruses.[4][5] Serpins are thus the largest and most diverse family of protease inhibitors.[6]
While most serpins control proteolytic cascades, certain serpins do not inhibit enzymes, but instead perform diverse functions such as storage (ovalbumin, in egg white), hormone carriage proteins (thyroxine-binding globulin, cortisol binding globulin) and tumor suppressor genes (maspin). The term serpin is used to describe these latter members as well, despite their noninhibitory function.[7]
As serpins control processes such as coagulation and inflammation, these proteins are the target of medical research. However, serpins are also of particular interest to the structural biology and protein folding communities, because they undergo a unique and dramatic change in shape (or conformational change) when they inhibit target proteases.[8] This is unusual - most classical protease inhibitors function as simple "lock and key" molecules that bind to and block access to the protease active site (see for example, bovine pancreatic trypsin inhibitor). While the serpin mechanism of protease inhibition confers certain advantages, it also has drawbacks and serpins are vulnerable to mutations that result in protein misfolding and the formation of inactive long chain polymers (serpinopathies).[9][10] Serpin polymerisation reduces the amount of active inhibitor, as well as accumulation of serpin polymers causing cell death and organ failure. For example, the serpin antitrypsin is primarily produced in the liver, and antitrypsin polymerisation causes liver cirrhosis.[10] Understanding serpinopathies also provides insights on protein misfolding in general, a process common to many human diseases, such as Alzheimer’s and CJD.[9]
# Proteases inhibited by serpins
Most inhibitory serpins target chymotrypsin-like serine proteases (see Table 1). These enzymes are defined by the presence of a nucleophilic serine residue in their catalytic site. Examples include thrombin, trypsin and human neutrophil elastase.[11]
Some serpins inhibit other classes of protease and are termed "cross class inhibitors". For example squamous cell carcinoma antigen 1 (SCCA-1) and the avian serpin myeloid and erythroid nuclear termination stage specific protein (MENT) both inhibit papain-like cysteine proteases[12][13][14]
The viral serpin crmA is a suppressor of the inflammatory response through inhibition of IL-1 and IL-18 processing by the cysteine protease caspase-1.[15] Cysteine proteases differ from serine proteases in that they are defined by the presence of a nucleophilic cysteine residue, rather than a serine residue, in their catalytic site.[16] Nonetheless, the enzymatic chemistry is similar, and serpins most likely inhibit both classes of enzyme in a similar fashion.[17]
# Localisation and general biological roles
Approximately two thirds of human serpins perform extracellular roles. For example, extracellular serpins regulate the proteolytic cascades central to blood clotting (antithrombin), the inflammatory response (antitrypsin, antichymotrypsin and C1 inhibitor) and tissue remodelling (PAI-1). Non-inhibitory extracellular serpins also perform important roles. Thyroxine-binding globulin and cortisol binding globulin transport the sterol hormones thyroxine and cortisol respectively.[18][1] The protease renin cleaves off a ten amino acid N-terminal peptide from angiotensinogen to produce the peptide hormone angiotensin I.[19] Table 1 at the bottom of this article provides a brief summary of human serpin function as well as some of the diseases that result from serpin deficiency.
The first Intracellular members of the serpin superfamily were identified in the early 1990s.[20][21] As all nine serpins in Caenorhabditis elegans lack signal sequences, they are probably intracellular.[22] Based upon these data it seems likely that the ancestral serpin to human serpins was an intracellular molecule.
The protease targets of intracellular inhibitory serpins have been more difficult to identify. Characterisation is complicated by these molecules appearing to perform overlapping roles, as well as the lack of precise functional equivalents of human serpins in model organisms such as the mouse. An important function of intracellular serpins may be to protect against the inappropriate activity of proteases inside the cell.[23] For example, one of the best characterised human intracellular serpins is SERPINB9, which inhibits the cytotoxic granule protease granzyme B. In doing so, SERPINB9 may protect against inadvertent release of granzyme B and premature or unwanted activation of cell death pathways.[24]
Intracellular serpins also perform roles distinct from protease inhibition. For example, maspin, a non-inhibitory serpin, is important for preventing metastasis in breast and prostate cancers.[25][26] Another example is the avian nuclear cysteine protease inhibitor MENT, which acts as a chromatin remodelling molecule in avian red blood cells.[27][13]
Phylogenetic studies show that most intracellular serpins belong to a single clade (see table 1). Exceptions include the non-inhibitory heat shock serpin HSP47, which is a chaperone essential for proper folding of collagen and cycles between the cis-Golgi and the endoplasmic reticulum.[28]
# Structure
Structural biology has played a central role in the understanding of serpin function and biology. Over eighty serpin structures, in a variety of different conformations (described below) have been determined to date. Although the function of serpins varies widely, these molecules all share a common structure (or fold).
The structure of the non-inhibitory serpin ovalbumin, and the inhibitory serpin antitrypsin revealed the archetype native serpin fold.[31][32] All typically have three β-sheets (termed A, B and C) and eight or nine α-helices (hA-hI) (see figure 1). Serpins also possess an exposed region termed the reactive centre loop (RCL) that in inhibitory molecules includes the specificity determining region and forms the initial interaction with the target protease. In antitrypsin, the RCL is held at the top of the molecule and is not pre-inserted into the A β-sheet (figure 1, left panel). This conformation commonly exists in dynamic equilibrium with a partially inserted native conformation[33] seen in other inhibitory serpins (see figure 1, right panel).
# Conformational change and inhibitory mechanism
Early studies on serpins revealed that the mechanism by which these molecules inhibit target proteases appeared distinct from the lock-and-key-type mechanism utilised by small protease inhibitors such as the Kunitz-type inhibitors (eg. Basic pancreatic protease inhibitor). Indeed, serpins form covalent complexes with target proteases.[34] Structural studies on serpins also revealed that inhibitory members of the family undergo an unusual conformational change, termed the Stressed to Relaxed (S to R) transition.[31][33][35][36] During this structural transition the RCL inserts into β-sheet A (in red in figure 1 and 2) and forms an extra (fourth) β-strand. The serpin conformational change is key to the mechanism of inhibition of target proteases.
When attacking a substrate, serine proteases catalyze peptide bond cleavage in a two-step process. Initially, the catalytic serine performs a nucleophilic attack on the peptide bond of the substrate (Figure 3). This releases the new N-terminus and forms an ester-bond between the enzyme and the substrate. This covalent enzyme-substrate complex is called an acyl enzyme intermediate. Subsequently, this ester bond is hydrolysed and the new C-terminus is released. The RCL of a serpin acts as a substrate for its cognate protease. However, after the RCL is cleaved, but prior to hydrolysis of the acyl-enzyme intermediate, the serpin rapidly undergoes the S to R transition. Since the RCL is still covalently attached to the protease via the ester bond, the S to R transition causes the protease to be moved from the top to the bottom of the serpin. At the same time, the protease is distorted into a conformation where the acyl enzyme intermediate is hydrolysed extremely slowly.[8] The protease thus remains covalently attached to the target protease and is thereby inhibited. Further, since the serpin has to be cleaved to inhibit the target protases, inhibition consumes the serpin as well. Serpins are therefore irreversible enzyme inhibitors. The serpin mechanism of inhibition is illustrated in figure 2 and several movies illustrating the serpin mechanism can be seen at this link.
# Conformational modulation of serpin activity
The conformational mobility of serpins provides a key advantage over static lock and key protease inhibitors. In particular, the function of inhibitory serpins can be readily controlled by specific cofactors. The X-ray crystal structures of antithrombin, heparin co-factor II, MENT and murine antichymotrypsin reveal that these serpins adopt a conformation where the first two amino acids of the RCL are inserted into the top of the A β-sheet (see figures 1 and 4). The partially inserted conformation is important because co-factors are able to conformationally switch partially inserted serpins into a fully expelled form.[38][39] This conformational rearrangement makes the serpin a more effective inhibitor.
The archetypal example of this situation is antithrombin, which circulates in plasma in a partially inserted relatively inactive state. The primary specificity determining residue (the P1 Arginine) points towards the body of the serpin and is unavailable to the protease (Figure 4). Upon binding a high affinity heparin pentasaccharide sequence within long chain heparin, antithrombin undergoes a conformational change, RCL expulsion and exposure of the P1 Arginine. The heparin pentasaccharide bound form of antithrombin is thus a more effective inhibitor of thrombin and factor Xa (figure 4).[40][41] Furthermore, both of these coagulation proteases contain binding sites (called exosites) for heparin. Heparin therefore also acts as a template for binding of both protease and serpin, further dramatically accelerating the interaction between the two parties (Figure 4). After the initial interaction, the final serpin complex is formed and the heparin moiety is released. This interaction is physiologically important. For example, after injury to the blood vessel wall heparin is exposed, and antithrombin is thus activated to control the clotting response. The understanding of the molecular basis of this interaction formed the basis of the development of Fondaparinux, a synthetic form of Heparin pentasaccharide used as an anti-clotting drug.[42]
Certain serpins spontaneously undergo the S to R transition as part of their function, to form a conformation termed the latent state (Figure 5). In latent serpins the first strand of the C-sheet has to peel off to allow full RCL insertion. Latent serpins are unable to interact with proteases and are not protease inhibitors. The transition to latency represents a control mechanism for the serpin PAI-1. PAI-1 is released in the inhibitory conformation, however, undergoes conformational change to the latent state unless it is bound to the cofactor vitronectin.[43] Thus PAI-1 contains an "auto-inactivation" mechanism. Similarly, antithrombin can also spontaneously convert to the latent state as part of its normal function. Finally, the N-terminus of tengpin[15][16], a serpin from Thermoanaerobacter tengcongensis, is required to lock the molecule in the native inhibitory state. Disruption of interactions made by the N-terminal region results in spontaneous conformational change of this serpin to the latent conformation.[44]
# Serpin receptor interactions
In humans, extracellular serpin-enzyme complexes are rapidly cleared from circulation. One mechanism by which this occurs is the low density lipoprotein receptor related protein (LRP receptor), which binds to inhibitory complexes made by antithrombin, PA1-1 and neuroserpin, causing uptake and subsequent signalling events.[45] Thus, as a consequence of the conformational change during serpin-enzyme complex formation, serpins may act as signalling molecules that alert cells to the presence of protease activity.[45] The fate of intracellular serpin-enzyme complexes remains to be characterised.
# Conformational change and non-inhibitory function
Certain non-inhibitory serpins also use the serpin conformational change as part of their function. For example the native (S) form of thyroxine-binding globulin has high affinity for thyroxine, whereas the cleaved (R) form has low affinity. Similarly, native (S) Cortisol Binding Globulin (CBG) has higher affinity for cortisol than its cleaved (R) counterpart. Thus, in these serpins, RCL cleavage and the S to R transition has been commandeered to allow for ligand release, rather than protease inhibition.[46][18][1]
# Serpins, serpinopathies and human disease
The complexity of the serpin mechanism renders these molecules vulnerable to inactivating mutations that promote inappropriate conformational change (or misfolding) and diseases ("serpinopathies"). Well characterised serpinopathies include emphysema, cirrhosis, thrombosis and dementia. Serpins thus belong to a large group of molecules such as the prion proteins and the glutamine repeat containing proteins that are susceptible to misfolding, causing conformational disease.[9]
The ability to map the mutations in serpins that cause serpinopathies onto a structural framework aided understanding of the mechanism of normal serpin conformational changes, as well as serpin dysfunction.[47] In particular, many serpin mutations that cause disease localise to two distinct regions of the molecule (highlighted in figure 1a) termed the shutter and the breach. The shutter and the breach contain highly-conserved residues and underlie the path of RCL insertion.
Serpin misfolding results in two common outcomes, both of which stem from the instability of the native (S) conformation. Firstly, pathogenic mutations in serpins can promote inappropriate transition to the monmoeric latent state. This causes disease because it reduces the amount of active inhibitory serpin. For example, the disease-linked antithrombin variants wibble and wobble,[48] both promote formation of the latent state.
Secondly, and more insidiously, mutations in serpins may cause polymerisation. While the X-ray crystal structure of an intact serpin polymer remains to be determined, much biochemical, biophysical and structural data suggest that serpins "domain swap" with one another and form long-chain polymers.[10][49][50] This may occur by a RCL of one serpin inserting into the A-sheet of another serpin, to form a chain, rather than inserting into its "own" A-sheet (see figure 6a for a model). The polymeric form is inactive and causes pathology. Serpin polymerisation causes disease in two ways. Firstly, the lack of active serpin results in uncontrolled protease activity and tissue destruction, this is seen in the case of antitrypsin deficiency. Secondly, the polymers themselves clog up the endoplasmic reticulum of cells that synthesize serpins, eventually resulting in cell death and tissue damage. In the case of antitrypsin deficiency, antitrypsin polymers cause the death of liver cells, eventually resulting in liver damage and cirrhosis.
.
Finally, it is worth highlighting a structure of a disease-linked human antichymotrypsin variant that demonstrates the extraordinary flexibility of the serpin scaffold. The structure of antichymotrypsin (Leucine 55 to Proline) revealed a novel "delta" conformation that may represent an intermediate between the native and latent state (Figure 6b). In the delta conformation four residues of the RCL are inserted into the top of β-sheet A. The bottom half of the sheet is filled as a result of one of the α-helices (the F-helix) partially switching to a strand-like conformation, completing the β-sheet hydrogen bonding.[52] It is unclear whether other serpins can adopt this conformer, or whether this conformation has a functional role. However, this conformation may be important for thyroxine release by Thyroxine binding globulin.[18]
# Other mechanisns of serpin-related disease
In humans, simple deficiency of many serpins (e.g. through a null mutation) may result in disease (see table 1).
Rarely, single amino acid changes in the RCL of a serpin alters the specificity of the inhibitor and allow it to target the wrong protease. For example, the Antitrypsin-Pittsburgh mutation (methionine 358 to arginine) allowed the serpin to inhibit thrombin, thus causing a bleeding disorder. [53]
Serpins are suicide inhibitors, the RCL acting as a "bait". Certain disease-linked mutations in the RCL of human serpins permit true substrate-like behaviour and cleavage without complex formation. Such variants are speculated to affect the rate or the extent of RCL insertion into the A-sheet. These mutations effectively result in serpin deficiency through a failure to properly control the target protease.[47][54]
Several non-inhibitory serpins play key roles in important human diseases. Most notably, maspin functions as a tumour suppressor in breast and prostate cancer. The mechanism of maspin function remains to be fully understood. Murine knockouts of maspin are lethal; these data suggest that maspin plays a key role in development.[55]
# Evolution
Serpins were initially believed to be restricted to eukaryote organisms, but have since been found in a number of bacteria and archaea.[4][5][56] It remains unclear whether these prokaryote genes are the descendants of an ancestral prokaryotic serpin or whether they are the product of lateral gene transfer (genetic transfer between organisms not by evolutionary descent). Rawlings et al., showed that serpins are the most widely distributed and largest family of protease inhibitors.[6]
# Types of serpins
## Human serpins
The human genome encodes 36 serpins (see Law et al., (2006) for a recent review.[57]). Table 1 lists each human serpin, together with brief notes in regards to each molecules function and the consequence (where known) of dysfunction or deficiency.
### Table 1
## Insect Serpins
Studies on Drosophila serpins reveal that Serpin-27A inhibits the Easter protease (the final protease in the Nudel, Gastrulation Defective, Snake and Easter proteolytic cascade) and thus controls dorsoventral patterning. Easter functions to cleave Spätzle (a chemokine-type ligand), which results in toll mediated signaling. In addition to its central role in embryonic patterning, toll signalling is also important for the innate immune response in insects. Accordingly, serpin-27A additionally functions to control the insect immune response.[95][96][97]
## Worm Serpins
The genome of the nematode worm C. elegans contains nine serpins, however, only five of these molecules appear to function as protease inhibitors. [22] One of these serpins, SRP-6, has been shown to perform a protective function and guard against stress induced calpain-associated lysosomal disruption. Further SRP-6 functions to inhibit lysosomal cysteine proteases released after lysosomal rupture. Accordingly, worms lacking SRP-6 are sensitive to stress. Most notably, SRP-6 knockout worms die when placed in water (the hypo-osmotic stress lethal phenotype or Osl). Based on these data it is suggested that lysosomes play a general and controllable role in determining cell fate. [98]
## Plant serpins
The presence of serpins in plants has long been recognised - indeed, barley Z serpin is the major protein component in beer. The genome sequence of Arabidopsis thaliana is predicted to encode 29 serpins. Plant serpins are able to inhibit serine proteases in vitro. However, the absence of close relatives of chymotrypsin-like proteases in plants suggests that these molecules may instead perform an alternative function. Indeed, Arabidopsis serpin1 inhibits metacaspase-like proteases in vivo and may control cell death pathways.[99]
## Prokaryote serpins
Predicted serpin genes are sporadicly distributed in prokaryotes. In vitro studies on some of these moelcules have revealed that they are able to inhibit proteases and it is suggested that they function as inhibitors in vivo. Interestingly, several prokaryote serpins are found in extremeophiles. Accordingly, and in contrast to mammalian serpins, these molecule possess elevated resistance to heat denaturation.[100][101] The precise role of most bacterial serpins remains obscure, however, Clostridium thermocellum serpin localises to the cellulosome, a large extracellular mulitprotein complex that breaks down cellulose. It is suggested that the role of cellulosome-associated serpins may be to prevent unwanted protease activity against the cellulosome.[102]
## Classification
In 2001, a serpin nomenclature was established.[7] The naming system is based upon a phylogenetic analysis of ~500 serpins.[4] This work classified the serpins into sixteen major clades, with several orphan sequences. The serpin family continues to grow - to date over 1000 serpins have been identified. | https://www.wikidoc.org/index.php/Serine_protease_inhibitor | |
71113f32dbac3044920e1904dc95454f19a32965 | wikidoc | Seroma | Seroma
A seroma is a pocket of clear serous fluid that sometimes develops in the body after surgery. When small blood vessels are ruptured, blood plasma can seep out; inflammation caused by dying injured cells also contributes to the fluid.
Seromas are different from hematomas which contain red blood cells and from abscesses which contain pus and result from an infection.
Seromas can sometimes be caused by a new type of partial-breast radiation therapy, as explained in a recent article in the International Journal of Radiation Oncology, Biology, Physics.
Seromas can also sometimes be caused by injury such as when the initial swelling from a blow or fall does not fully subside. The remaining serous fluid causes a seroma that the body usually gradually absorbs over time (often taking many weeks); however, a knot of calcified tissue sometimes remains.
Seroma is particularly common after mastectomy surgery for breast cancer and many women find that it makes their initial recovery period more difficult. Some women need repeated visits to their doctor to have the seroma fluid drained. | Seroma
A seroma is a pocket of clear serous fluid that sometimes develops in the body after surgery. When small blood vessels are ruptured, blood plasma can seep out; inflammation caused by dying injured cells also contributes to the fluid.
Seromas are different from hematomas which contain red blood cells and from abscesses which contain pus and result from an infection.
Seromas can sometimes be caused by a new type of partial-breast radiation therapy, as explained in a recent article in the International Journal of Radiation Oncology, Biology, Physics.
Seromas can also sometimes be caused by injury such as when the initial swelling from a blow or fall does not fully subside. The remaining serous fluid causes a seroma that the body usually gradually absorbs over time (often taking many weeks); however, a knot of calcified tissue sometimes remains.
Seroma is particularly common after mastectomy surgery for breast cancer and many women find that it makes their initial recovery period more difficult. Some women need repeated visits to their doctor to have the seroma fluid drained. [1]
[2]
[3]
Template:WH
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Seroma | |
588a16db5731c75227768fc2d3702b9a7b77a3bb | wikidoc | Sesame | Sesame
Sesame (Sesamum indicum) is a flowering plant in the genus Sesamum. The precise natural origin of the species is unknown, although numerous wild relatives occur in Africa and a smaller number in India. It is widely naturalised in tropical regions around the world and is cultivated for its edible seeds.
It is an annual plant growing to 50 to 100 cm (2-3 feet) tall, with opposite leaves 4 to 14 cm (5.5 in) long with an entire margin; they are broad lanceolate, to 5 cm (2 in) broad, at the base of the plant, narrowing to just 1 cm (half an inch) broad on the flowering stem. The flowers are white to purple, tubular, 3 to 5 cm (1 to 2 in) long, with a four-lobed mouth.
# Origins
Despite the fact that the majority of the wild species of the genus Sesamum are native to sub-saharan Africa, Zohary and Hopf argue that sesame was first domesticated in India. They cite morphological and cytogenetic affinities between domesticated sesame and the south Indian native S. mulayanum Nair., as well as archeological evidence that it was cultivated at Harappa in the Indus Valley between 2250 and 1750 BC, and a more recent find of charred sesame seeds in Miri Qalat and Shahi Tump in the Makran region of Pakistan. They regard the identification of sesame seeds in the finds from the tomb of Tutankhamun from ancient Egypt "might be true, but are in need of further verification."
## Etymology
The word sesame is from Latin sesamum, borrowed from Greek sēsámon "seed or fruit of the sesame plant", borrowed from Semitic (cf. Aramaic shūmshĕmā, Arabic simsim), from Late Babylonian *shawash-shammu, itself from Assyrian shamash-shammū, from shaman shammī "plant oil".
In India, where sesame is cultivated since the Harappan period, there are two independent names for it: Sanskrit tila (Hindi/Urdu til ) is the source of all names in North India and In contrast, most of the Dravidian languages in South India feature an independent name for sesame exemplified by Tamil, Malayalam and Kannada ellu .
From all the 3 roots above, words with the generalized meaning “oil; liquid fat” are derived, e.g., Sanskrit taila . Similar semantic shifts from the name of an oil crop to a general word “fat, oil” are also known for other languages, e.g., “olive” has given rise to English “oil”.
In some languages of the Middle East, sesame is named differently and evolved from Middle Persian kunjid. This has been imported into a few western languages - ex. Russian kunzhut , Estonian kunžuut and Yiddish kunzhut .
Portuguese (Brazil only) gergelim and Spanish ajonjolí and Hindi gingli derive from an Arabic noun jaljala “sound, echo”, referring to the rattling sound of ripe seeds within the capsule.
In southern US and the Carribbean, where the sesame seed was introduced by Slaves imported from Africa, it is also known by the african name Benne.
## Mythological background
According to Assyrian legend, when the gods met to create the world, they drank wine made from sesame seeds. In early Hindu legends, tales are told in which sesame seeds represent a symbol of immortality. "Open sesame," the famous phrase from the Arabian Nights, reflects the distinguishing feature of the sesame seed pod, which bursts open when it reaches maturity..
It is also used in Urdu literature as proverbs "til dharnay ki jagah na hona"; meaning by, a place so crowded that there is no room for a single seed of sesame and "in tilon mein teil nahee" (ان تلوں میں تیل نہیں); referred for a person who is very mean, meaning by there is no oil left in this sesame.
# Uses in food and cuisines
Sesame is grown primarily for its oil-rich seeds, which come in a variety of colors, from cream-white to charcoal-black. In general, the paler varieties of sesame seem to be more valued in the West and Middle East, while the black varieties are prized in the Far East.
The small sesame seed is used whole in cooking for its rich nutty flavour (although such heating damages their healthful poly-unsaturated fats), and also yields sesame oil.
Sesame seeds are sometimes added to breads, including bagels and the tops of hamburger buns. Sesame seeds may be baked into crackers, often in the form of sticks. Sesame seeds are also sprinkled onto some sushi style foods. Whole seeds are found in many salads and baked snacks as well in Japan. Tan and black sesame seed varieties are roasted and used for making the flavoring gomashio. In Greece seeds are used in cakes, while in Togo, seeds are a main soup ingredient. The seeds are also eaten on bread in Sicily. About one-third of the sesame crop imported by the United States from Mexico is purchased by McDonald's for their sesame seed buns (The Nut Factory 1999). In Punjab province of Pakistan and Tamil Nadu state of India, a sweet ball called "Pinni" (پنی) in Urdu and 'Ell urundai' in Tamil, is made of its seeds mixed with sugar. Also in Tamil Nadu, 'Milakai Podi', a nice grounded powder made of sesame and dry chilly is used to enhance flavour and consumed along with other traditional foods such as idli.
Ground and processed, the seeds can also be used in sweet confections. Sesame seeds can be made into a paste called tahini (used in various ways, including in hummus) and a Middle Eastern confection called halvah. In India, sections of the Middle East, and East Asia, popular treats are made from sesame mixed with honey or syrup and roasted (called pasteli in Greece). In Japanese cuisine goma-dofu (胡麻豆腐) is made from sesame paste and starch.
East Asian cuisines, like Chinese cuisine use sesame seeds and oil in some dishes, such as the dim sum dish, sesame seed balls (Template:Zh-tp or 煎堆; Cantonese: jin deui), and the Vietnamese bánh rán. Sesame flavour (through oil and roasted or raw seeds) is also very popular in Korean cuisine, used to marinate meat and vegetables. Chefs in tempura restaurants blend sesame and cottonseed oil for deep-frying. Sesame oil was the preferred cooking oil in India until the advent of groundnut (peanut) oil.
Although sesame leaves are edible as a potherb, recipes for Korean cuisine calling for "sesame leaves" are often a mistranslation, and really mean perilla.
- A simit is a small circular Turkish bread with sesame seeds
A simit is a small circular Turkish bread with sesame seeds
- Thai workers harvesting sesame
Thai workers harvesting sesame
- Dry sesame seeds
Dry sesame seeds
# Nutrition and health treatments
The seeds are rich in manganese, copper, and calcium (90 mg per tablespoon for unhulled seeds, 10 mg for hulled), and contain vitamin B1 (thiamine) and vitamin E (tocopherol). They contain lignans, including unique content of sesamin, which are phytoestrogens with antioxidant and anti-cancer properties. Among edible oils from six plants, sesame oil had the highest antioxidant content.
Sesame seeds also contain phytosterols associated with reduced levels of blood cholesterol, but do not contain caffeine. The nutrients of sesame seeds are better absorbed if they are ground or pulverized before consumption.
Women of ancient Babylon would eat halva, a mixture of honey and sesame seeds to prolong youth and beauty, while Roman soldiers ate the mixture for strength and energy .
While sesame seeds are generally considered nutritious, they produce one of the most common food allergies.
There have been erroneous claims that sesame seeds also contain THC which may be detectable on random screening. This error stems from a misunderstanding of the commercial drug Dronabinol, a synthetic form of THC. The normal delivery mechanism for synthetic Dronabinol is via infusion into sesame oil and encapsulation into soft gelatin capsules. As a result some people are under the mistaken assumption that sesame oil naturally contains THC.
Sesame oil is used for massage and health treatments of the body in the ancient Indian ayurvedic system with the types of massage called abhyanga and shirodhara. Ayurveda views sesame oil as the most viscous of the plant oils and believes it may pacify the health problems associated with Vata aggravation.
# Cultivation
Sesame is grown in many parts of the world on over 5 million acres (20,000 km²). The biggest area of production is currently believed to be India, but the crop is also grown in China, Burma, Sudan, Mexico and Ethiopia et al. US commercial production reportedly began in the 1950s. Area in the U.S., primarily in Texas and southwestern states, has ranged from 10,000 to 20,000 acres (40 to 80 km²) in recent years; however, the U.S. imports more sesame than it grows.
Pests
Sesame is used as a food plant by the larvae of some Lepidoptera species, including the Turnip Moth. | Sesame
Sesame (Sesamum indicum) is a flowering plant in the genus Sesamum. The precise natural origin of the species is unknown, although numerous wild relatives occur in Africa and a smaller number in India. It is widely naturalised in tropical regions around the world and is cultivated for its edible seeds.
It is an annual plant growing to 50 to 100 cm (2-3 feet) tall, with opposite leaves 4 to 14 cm (5.5 in) long with an entire margin; they are broad lanceolate, to 5 cm (2 in) broad, at the base of the plant, narrowing to just 1 cm (half an inch) broad on the flowering stem. The flowers are white to purple, tubular, 3 to 5 cm (1 to 2 in) long, with a four-lobed mouth.
# Origins
Despite the fact that the majority of the wild species of the genus Sesamum are native to sub-saharan Africa, Zohary and Hopf argue that sesame was first domesticated in India. They cite morphological and cytogenetic affinities between domesticated sesame and the south Indian native S. mulayanum Nair., as well as archeological evidence that it was cultivated at Harappa in the Indus Valley between 2250 and 1750 BC, and a more recent find of charred sesame seeds in Miri Qalat and Shahi Tump in the Makran region of Pakistan. They regard the identification of sesame seeds in the finds from the tomb of Tutankhamun from ancient Egypt "might be true, but are in need of further verification."[1]
## Etymology
The word sesame is from Latin sesamum, borrowed from Greek sēsámon "seed or fruit of the sesame plant", borrowed from Semitic (cf. Aramaic shūmshĕmā, Arabic simsim), from Late Babylonian *shawash-shammu, itself from Assyrian shamash-shammū, from shaman shammī "plant oil".
In India, where sesame is cultivated since the Harappan period, there are two independent names for it: Sanskrit tila [तिल] (Hindi/Urdu til [तिल, تل]) is the source of all names in North India and In contrast, most of the Dravidian languages in South India feature an independent name for sesame exemplified by Tamil, Malayalam and Kannada ellu [எள்ளு, ಎಳ್ಳು].
From all the 3 roots above, words with the generalized meaning “oil; liquid fat” are derived, e.g., Sanskrit taila [तैल]. Similar semantic shifts from the name of an oil crop to a general word “fat, oil” are also known for other languages, e.g., “olive” has given rise to English “oil”.
In some languages of the Middle East, sesame is named differently and evolved from Middle Persian kunjid. This has been imported into a few western languages - ex. Russian kunzhut [кунжут], Estonian kunžuut and Yiddish kunzhut [קונזשוט].
Portuguese (Brazil only) gergelim and Spanish ajonjolí and Hindi gingli [गिंगली] derive from an Arabic noun jaljala [جلجلة] “sound, echo”, referring to the rattling sound of ripe seeds within the capsule.[2]
In southern US and the Carribbean, where the sesame seed was introduced by Slaves imported from Africa, it is also known by the african name Benne.
## Mythological background
According to Assyrian legend, when the gods met to create the world, they drank wine made from sesame seeds. In early Hindu legends, tales are told in which sesame seeds represent a symbol of immortality. "Open sesame," the famous phrase from the Arabian Nights, reflects the distinguishing feature of the sesame seed pod, which bursts open when it reaches maturity.[3].
It is also used in Urdu literature as proverbs "til dharnay ki jagah na hona"; meaning by, a place so crowded that there is no room for a single seed of sesame and "in tilon mein teil nahee" (ان تلوں میں تیل نہیں); referred for a person who is very mean, meaning by there is no oil left in this sesame.
# Uses in food and cuisines
Sesame is grown primarily for its oil-rich seeds, which come in a variety of colors, from cream-white to charcoal-black. In general, the paler varieties of sesame seem to be more valued in the West and Middle East, while the black varieties are prized in the Far East.
The small sesame seed is used whole in cooking for its rich nutty flavour (although such heating damages their healthful poly-unsaturated fats), and also yields sesame oil.
Sesame seeds are sometimes added to breads, including bagels and the tops of hamburger buns. Sesame seeds may be baked into crackers, often in the form of sticks. Sesame seeds are also sprinkled onto some sushi style foods. Whole seeds are found in many salads and baked snacks as well in Japan. Tan and black sesame seed varieties are roasted and used for making the flavoring gomashio. In Greece seeds are used in cakes, while in Togo, seeds are a main soup ingredient. The seeds are also eaten on bread in Sicily. About one-third of the sesame crop imported by the United States from Mexico is purchased by McDonald's for their sesame seed buns (The Nut Factory 1999).[4] In Punjab province of Pakistan and Tamil Nadu state of India, a sweet ball called "Pinni" (پنی) in Urdu and 'Ell urundai' in Tamil, is made of its seeds mixed with sugar. Also in Tamil Nadu, 'Milakai Podi', a nice grounded powder made of sesame and dry chilly is used to enhance flavour and consumed along with other traditional foods such as idli.
Ground and processed, the seeds can also be used in sweet confections. Sesame seeds can be made into a paste called tahini (used in various ways, including in hummus) and a Middle Eastern confection called halvah. In India, sections of the Middle East, and East Asia, popular treats are made from sesame mixed with honey or syrup and roasted (called pasteli in Greece). In Japanese cuisine goma-dofu (胡麻豆腐) is made from sesame paste and starch.
East Asian cuisines, like Chinese cuisine use sesame seeds and oil in some dishes, such as the dim sum dish, sesame seed balls (Template:Zh-tp or 煎堆; Cantonese: jin deui), and the Vietnamese bánh rán. Sesame flavour (through oil and roasted or raw seeds) is also very popular in Korean cuisine, used to marinate meat and vegetables. Chefs in tempura restaurants blend sesame and cottonseed oil for deep-frying. Sesame oil was the preferred cooking oil in India until the advent of groundnut (peanut) oil.
Although sesame leaves are edible as a potherb[1], recipes for Korean cuisine calling for "sesame leaves" are often a mistranslation, and really mean perilla[2].
- A simit is a small circular Turkish bread with sesame seeds
A simit is a small circular Turkish bread with sesame seeds
- Thai workers harvesting sesame
Thai workers harvesting sesame
- Dry sesame seeds
Dry sesame seeds
# Nutrition and health treatments
The seeds are rich in manganese, copper, and calcium (90 mg per tablespoon[5] for unhulled seeds, 10 mg for hulled), and contain vitamin B1 (thiamine) and vitamin E (tocopherol).[6] They contain lignans, including unique content of sesamin, which are phytoestrogens with antioxidant and anti-cancer properties. Among edible oils from six plants, sesame oil had the highest antioxidant content[7].
Sesame seeds also contain phytosterols associated with reduced levels of blood cholesterol, but do not contain caffeine. The nutrients of sesame seeds are better absorbed if they are ground or pulverized before consumption.
Women of ancient Babylon would eat halva, a mixture of honey and sesame seeds to prolong youth and beauty, while Roman soldiers ate the mixture for strength and energy [8].
While sesame seeds are generally considered nutritious, they produce one of the most common food allergies.
There have been erroneous claims that sesame seeds also contain THC which may be detectable on random screening. This error stems from a misunderstanding of the commercial drug Dronabinol, a synthetic form of THC. The normal delivery mechanism for synthetic Dronabinol is via infusion into sesame oil and encapsulation into soft gelatin capsules. As a result some people are under the mistaken assumption that sesame oil naturally contains THC.
Sesame oil is used for massage and health treatments of the body in the ancient Indian ayurvedic system with the types of massage called abhyanga and shirodhara. Ayurveda views sesame oil as the most viscous of the plant oils and believes it may pacify the health problems associated with Vata aggravation.
# Cultivation
Sesame is grown in many parts of the world on over 5 million acres (20,000 km²). The biggest area of production is currently believed to be India, but the crop is also grown in China, Burma, Sudan, Mexico and Ethiopia et al. US commercial production reportedly began in the 1950s. Area in the U.S., primarily in Texas and southwestern states, has ranged from 10,000 to 20,000 acres (40 to 80 km²) in recent years; however, the U.S. imports more sesame than it grows.[9]
Pests
Sesame is used as a food plant by the larvae of some Lepidoptera species, including the Turnip Moth. | https://www.wikidoc.org/index.php/Sesame | |
36e57fc808fdde57caf90574a168ed56c8a605d3 | wikidoc | Sewage | Sewage
Sewage is the mainly liquid waste containing some solids produced by humans which typically consists of washing water, faeces, urine, laundry waste and other material which goes down drains and toilets from households and industry. It is one type of wastewater. Sewage services exist to manage sewage by collection, treatment and recycling or safe disposal into the environment. As of 2004 in the U.S., 850 billion gallons of raw sewage are being dumped into waterways every year.
# History
According to Teresi et al. (2002):
The Indus architects designed sewage disposal systems on a large scale, building networks of brick effluent drains following the lines of the streets. The drains were seven to ten feet wide, cut at two feet below ground level with U-shaped bottoms lined with loose brick easily taken up for cleaning. At the intersection of two drains, the sewage planners installed cesspools with steps leading down into them, for periodic cleaning. By 2700 B.C., these cities had standardized earthenware plumbing pipes with broad flanges for easy joining with asphalt to stop leaks.
The first sanitation system have been found at the prehistoric Middle East and the surrounding areas. The first time an inverted siphon system was used, along with glass covered clay pipes, was in the palaces of Crete, Greece. It is still in working condition, after about 3000 years. The system then remained with not much progress until the 16th century, where, in England, Sir John Harington invented a device for Queen Elizabeth (his Godmother) that released wastes into cesspools.
# Sewage services
### Collection and disposal
A system of sewer pipes (sewers) collects sewage and takes it for treatment or disposal. The system of sewers is called sewerage or sewerage system (see London sewerage system) in UK English and sewage system in US English. Where a main sewerage system has not been provided, sewage may be collected from homes by pipes into septic tanks or cesspits, where it may be treated or collected in vehicles and taken for treatment or disposal.
Properly functioning septic tanks require emptying every 2-5 years depending on the load of the system.
### Treatment
Sewage treatment is the process of removing the contaminants from sewage to produce liquid and solid (sludge) suitable for discharge to the environment or for reuse. It is a form of waste management. A septic tank or other on-site wastewater treatment system such as biofilters can be used to treat sewage close to where it is created.
Sewage water is a complex matrix, with many distinctive chemical characteristics. These include high concentrations of ammonium, nitrate, phosphorus, high conductivity (due to high dissolved solids), high alkalinity, with pH typically ranging between 7 and 8. Trihalomethanes are also likely to be present as a result of past disinfection.
In developed countries sewage collection and treatment is typically subject to local, state and federal regulations and standards.
# Facts about sewage
- The words 'sewage' and 'sewer' come from Old French seuwiere or from Anglo-Norman sewere or from Anglo-French assewer, essiver meaning "(channel) to drain the overflow from a fish pond" or "to drain" and ultimately from Vulgar Latin *exaquare or *exaquria, from Latin ex- ‘out of’ + aqua ‘water’.
- The words 'sewerage' and 'sewage' were used interchangeably (but wrongly) in the past. This use is correct in US English. | Sewage
Sewage is the mainly liquid waste containing some solids produced by humans which typically consists of washing water, faeces, urine, laundry waste and other material which goes down drains and toilets from households and industry. It is one type of wastewater. Sewage services exist to manage sewage by collection, treatment and recycling or safe disposal into the environment. As of 2004 in the U.S., 850 billion gallons of raw sewage are being dumped into waterways every year.[1]
# History
According to Teresi et al. (2002):[2]
The Indus architects designed sewage disposal systems on a large scale, building networks of brick effluent drains following the lines of the streets. The drains were seven to ten feet wide, cut at two feet below ground level with U-shaped bottoms lined with loose brick easily taken up for cleaning. At the intersection of two drains, the sewage planners installed cesspools with steps leading down into them, for periodic cleaning. By 2700 B.C., these cities had standardized earthenware plumbing pipes with broad flanges for easy joining with asphalt to stop leaks.
The first sanitation system have been found at the prehistoric Middle East and the surrounding areas. The first time an inverted siphon system was used, along with glass covered clay pipes, was in the palaces of Crete, Greece. It is still in working condition, after about 3000 years. The system then remained with not much progress until the 16th century, where, in England, Sir John Harington invented a device for Queen Elizabeth (his Godmother) that released wastes into cesspools.
# Sewage services
### Collection and disposal
A system of sewer pipes (sewers) collects sewage and takes it for treatment or disposal. The system of sewers is called sewerage or sewerage system (see London sewerage system) in UK English and sewage system in US English. Where a main sewerage system has not been provided, sewage may be collected from homes by pipes into septic tanks or cesspits, where it may be treated or collected in vehicles and taken for treatment or disposal.
Properly functioning septic tanks require emptying every 2-5 years depending on the load of the system.
### Treatment
Sewage treatment is the process of removing the contaminants from sewage to produce liquid and solid (sludge) suitable for discharge to the environment or for reuse. It is a form of waste management. A septic tank or other on-site wastewater treatment system such as biofilters can be used to treat sewage close to where it is created.
Sewage water is a complex matrix, with many distinctive chemical characteristics. These include high concentrations of ammonium, nitrate, phosphorus, high conductivity (due to high dissolved solids), high alkalinity, with pH typically ranging between 7 and 8. Trihalomethanes are also likely to be present as a result of past disinfection.
In developed countries sewage collection and treatment is typically subject to local, state and federal regulations and standards.
# Facts about sewage
- The words 'sewage' and 'sewer' come from Old French seuwiere or from Anglo-Norman sewere or from Anglo-French assewer, essiver meaning "(channel) to drain the overflow from a fish pond" or "to drain" and ultimately from Vulgar Latin *exaquare or *exaquria, from Latin ex- ‘out of’ + aqua ‘water’.[1]
- The words 'sewerage' and 'sewage' were used interchangeably (but wrongly) in the past. This use is correct in US English.[2][3] | https://www.wikidoc.org/index.php/Sewage | |
e4e3a42b32235595d4095dd23bce70e934807c52 | wikidoc | Shower | Shower
A shower is a process of bathing by application of sprayed water upon the body; the term also refers the component of a typical modern bathroom that provides such a function. It offers an effective method of personal hygiene through a spraying of the body with hot or cold water as desired, often in combination with soap, shampoo or shower gel. It is also a more efficient use of water and the power necessary to heat it than taking a bath. By definition, a half bathroom does not include a shower; a full bath may include a full shower.
# History
The hygiene regimen in the form of a shower goes back to the time of the Greeks, as evidenced by extant vases and murals.
During the Scottish Enlightenment Lord Monboddo showered every morning with cold water on his front porch to emulate the Greeks and profess his belief in the practice as healthful; his habit, while eccentric, was well publicized with the intelligentsia of that era. Another step toward the spread of showering was when the Prussian military installed showering rooms in their barracks in 1879.
# Cultural significance
Showering in the Western World is mostly part of a daily routine, but is also practiced for wellness and relaxation. Showering has today largely replaced bathing. Many households today no longer own a bathtub, and thus use a shower to rinse their bodies.
# Showering procedure
Showering results in a few phases, in which the skin, and usually the hair, are wet with water. Then the cleansing products are applied, allowed to work, and subsequently rinsed out. If necessary, soaping and rinsing is re-performed.
Too frequent showering with cleansing products can damage the skin and hair. In order to protect the hair, a shower cap may be used.
Constant use of soaps or soap-based products in the shower can produce soap scum on the walls or floors, caused by the reaction of soap with lime in hard water. One of the advantages of using a shower gel instead of soap is that this soap scum does not form, reducing cleaning and maintenance of the shower.
# Elderly and disabled
Showering is easier and securer than bathtubing, for elderly and disabled people.
# Purpose
Various purposes of showering include routine hygiene, as well as safety (as in chemical spills, mass decontamination, etc.).
# Structure and designs
There are free-standing showers, but also showers which are integrated into a bathtub. Showers are separated from the surrounding area through watertight curtains (shower curtain), sliding doors, or folding doors, in order to protect the space from spraying water. There are seldom floor-level showers. Here, the wall and floor of the shower areas are tiled or otherwise made waterproof.
Places such as a swimming pool, a locker room, and a military facility, have multiple showers. There may be shower rooms without divisions (typically sex-segregated) or shower stalls (typically open at the top; often in shower rooms which are sex-segregated anyway).
Anthony David Rueli of the University of Massachusetts researched the aspect of why shower curtains billow inwards during showering ("shower-curtain effect") and received for it the Ig Nobel Prize in 2001.
A shower head is a perforated nozzle that showers water on a bather. They can be modified to spray different patterns of water. Due to hard water, calcium and magnesium often cake and dry on it, causing it to malfunction. | Shower
Template:Copyedit
A shower is a process of bathing by application of sprayed water upon the body; the term also refers the component of a typical modern bathroom that provides such a function. It offers an effective method of personal hygiene through a spraying of the body with hot or cold water as desired, often in combination with soap, shampoo or shower gel. It is also a more efficient use of water and the power necessary to heat it than taking a bath. By definition, a half bathroom does not include a shower; a full bath may include a full shower.
# History
The hygiene regimen in the form of a shower goes back to the time of the Greeks, as evidenced by extant vases and murals.[1]
During the Scottish Enlightenment Lord Monboddo showered every morning with cold water on his front porch to emulate the Greeks and profess his belief in the practice as healthful;[1] his habit, while eccentric, was well publicized with the intelligentsia of that era. Another step toward the spread of showering was when the Prussian military installed showering rooms in their barracks in 1879.
Template:Sect-stub
# Cultural significance
Showering in the Western World is mostly part of a daily routine, but is also practiced for wellness and relaxation. Showering has today largely replaced bathing. Many households today no longer own a bathtub, and thus use a shower to rinse their bodies.[citation needed]
# Showering procedure
Showering results in a few phases, in which the skin, and usually the hair, are wet with water. Then the cleansing products are applied, allowed to work, and subsequently rinsed out. If necessary, soaping and rinsing is re-performed.
Too frequent showering with cleansing products can damage the skin and hair. In order to protect the hair, a shower cap may be used.
Constant use of soaps or soap-based products in the shower can produce soap scum on the walls or floors, caused by the reaction of soap with lime in hard water. One of the advantages of using a shower gel instead of soap is that this soap scum does not form, reducing cleaning and maintenance of the shower.[citation needed]
# Elderly and disabled
Showering is easier and securer than bathtubing, for elderly and disabled people.
Template:Sectstub
# Purpose
Various purposes of showering include routine hygiene, as well as safety (as in chemical spills, mass decontamination, etc.).
# Structure and designs
There are free-standing showers, but also showers which are integrated into a bathtub. Showers are separated from the surrounding area through watertight curtains (shower curtain), sliding doors, or folding doors, in order to protect the space from spraying water. There are seldom floor-level showers. Here, the wall and floor of the shower areas are tiled or otherwise made waterproof.
Places such as a swimming pool, a locker room, and a military facility, have multiple showers. There may be shower rooms without divisions (typically sex-segregated) or shower stalls (typically open at the top; often in shower rooms which are sex-segregated anyway).
Anthony David Rueli of the University of Massachusetts researched the aspect of why shower curtains billow inwards during showering ("shower-curtain effect") and received for it the Ig Nobel Prize in 2001.
A shower head is a perforated nozzle that showers water on a bather. They can be modified to spray different patterns of water. Due to hard water, calcium and magnesium often cake and dry on it, causing it to malfunction. | https://www.wikidoc.org/index.php/Shower | |
062cd567b28b1cb0430644831293cdd353ecfa6a | wikidoc | Silane | Silane
# Overview
Silane is a chemical compound with chemical formula SiH4. It is the silicon analogue of methane. At room temperature, silane is a gas, and is pyrophoric — it undergoes spontaneous combustion in air, without the need for external ignition. However, the difficulties in explaining the available (often contradictory) combuistion data are ascribed to the fact that silane itself is stable and that the natural formation of larger silanes during production, as well as the sensitivity of combustion to impurities such as moisture and to the catalytic effects of container surfaces causes its pyrophoricity. Above 420°C, silane decomposes into silicon and hydrogen; it can therefore be used in the chemical vapor deposition of silicon.
More generally, a silane is any silicon analogue of an alkane hydrocarbon. Silanes consist of a chain of silicon atoms covalently bound to hydrogen atoms. The general formula of a silane is SinH2n+2. Silanes tend to be less stable than their carbon analogues because the Si–Si bond has a strength slightly lower than the C–C bond. Oxygen decomposes silanes easily, because the silicon-oxygen bond is quite stable.
There exists a regular nomenclature for silanes. Each silane's name is the word silane preceded by a numerical prefix (di, tri, tetra, etc.) for the number of silicon atoms in the molecule. Thus Si2H6 is disilane, Si3H8 is trisilane, and so forth. There is no need for a prefix for one; SiH4 is simply silane. Silanes can also be named like any other inorganic compound; in this naming system, silane is named silicon tetrahydride. However, with longer silanes, this becomes cumbersome.
A cyclosilane is a silane in a ring, just as a cycloalkane is an alkane in a ring.
Branched silanes are possible. The radical ·SiH3 is termed silyl, ·Si2H5 is disilanyl, and so on. Trisilane with a silyl group attached to the middle silicon is named silyltrisilane. The nomenclature parallels that of alkyl radicals.
Silanes can also incorporate the same functional groups as alkanes, e.g. –OH to make a silanol. There is (at least in principle) a silicon analogue for all carbon alkanes.
# Production
Industrially, silane is produced from metallurgical grade silicon in a two-step process. In the first step, powdered silicon is reacted with hydrogen chloride at about 300°C to produce trichlorosilane, HSiCl3, along with hydrogen gas, according to the chemical equation:
The trichlorosilane is then boiled on a resinous bed containing a catalyst which promotes its disproportionation to silane and silicon tetrachloride according to the chemical equation:
The most commonly used catalysts for this process are metal halides, particularly aluminium chloride.
# Properties
Silane has a repulsive smell.
Silane has recently been shown to act as superconductor under extremely high pressures (96 and 120 GPa), with a transition temperature of 17 K. Unfortunately, there was briefly an EE Times article that grossly exaggerated this achievement and claimed that room-temperature superconductivity had been achieved.
# Applications
Several industrial and medical applications exist for silanes. For instance, silanes are used as coupling agents to adhere glass fibers to a polymer matrix, stabilizing the composite material. They can also be used to couple a bio-inert layer on a titanium implant. Other applications include water repellents, masonry protection, control of graffiti, applying polycrystalline silicon layers on silicon wafers when manufacturing semiconductors, and sealants. Semiconductor industry alone used about 300 metric tons per year of silane in the late 1990s. More recently, a growth in low-cost solar panel manufacturing has lead to substantial consumption of silane for depositing amorphous silicon on glass and other surfaces.
Silane is also used in supersonic combustion ramjets to initiate combustion in the compressed air stream.
Silane and similar compounds containing Si-H-bonds are used as reducing agents in organic and organometallic chemistry.
"Mars sand" exposes regular sand to trimethylhydroxysilane vapors to make the sand waterproof.
Silane may be used to fabricate a super-compressed, superconducting compound.
# Safety and precautions
A number of fatal industrial accidents produced by detonation and combustion of leaked silane in air have been reported. Dilute silane mixtures with inert gases such as nitrogen or argon are even more likely to ignite when leaked into open air, compared to pure silane: even a 1% mixture of silane in pure nitrogen easily ignites when exposed to air. Unlike methane, silane is also fairly toxic: the lethal concentration in air for rats (LC50) is 0.96% over a 4-hour exposure. In addition, contact with eyes may form silicic acid with resultant irritation. | Silane
Template:Chembox new
# Overview
Silane is a chemical compound with chemical formula SiH4. It is the silicon analogue of methane. At room temperature, silane is a gas, and is pyrophoric — it undergoes spontaneous combustion in air, without the need for external ignition.[1] However, the difficulties in explaining the available (often contradictory) combuistion data are ascribed to the fact that silane itself is stable and that the natural formation of larger silanes during production, as well as the sensitivity of combustion to impurities such as moisture and to the catalytic effects of container surfaces causes its pyrophoricity.[2][3] Above 420°C, silane decomposes into silicon and hydrogen; it can therefore be used in the chemical vapor deposition of silicon.
More generally, a silane is any silicon analogue of an alkane hydrocarbon. Silanes consist of a chain of silicon atoms covalently bound to hydrogen atoms. The general formula of a silane is SinH2n+2. Silanes tend to be less stable than their carbon analogues because the Si–Si bond has a strength slightly lower than the C–C bond. Oxygen decomposes silanes easily, because the silicon-oxygen bond is quite stable.
There exists a regular nomenclature for silanes. Each silane's name is the word silane preceded by a numerical prefix (di, tri, tetra, etc.) for the number of silicon atoms in the molecule. Thus Si2H6 is disilane, Si3H8 is trisilane, and so forth. There is no need for a prefix for one; SiH4 is simply silane. Silanes can also be named like any other inorganic compound; in this naming system, silane is named silicon tetrahydride. However, with longer silanes, this becomes cumbersome.
A cyclosilane is a silane in a ring, just as a cycloalkane is an alkane in a ring.
Branched silanes are possible. The radical ·SiH3 is termed silyl, ·Si2H5 is disilanyl, and so on. Trisilane with a silyl group attached to the middle silicon is named silyltrisilane. The nomenclature parallels that of alkyl radicals.
Silanes can also incorporate the same functional groups as alkanes, e.g. –OH to make a silanol. There is (at least in principle) a silicon analogue for all carbon alkanes.
# Production
Industrially, silane is produced from metallurgical grade silicon in a two-step process. In the first step, powdered silicon is reacted with hydrogen chloride at about 300°C to produce trichlorosilane, HSiCl3, along with hydrogen gas, according to the chemical equation:
The trichlorosilane is then boiled on a resinous bed containing a catalyst which promotes its disproportionation to silane and silicon tetrachloride according to the chemical equation:
The most commonly used catalysts for this process are metal halides, particularly aluminium chloride.
# Properties
Silane has a repulsive smell.[4]
Silane has recently been shown to act as superconductor under extremely high pressures (96 and 120 GPa), with a transition temperature of 17 K.[5] Unfortunately, there was briefly an EE Times article that grossly exaggerated this achievement and claimed that room-temperature superconductivity had been achieved.
# Applications
Several industrial and medical applications exist for silanes. For instance, silanes are used as coupling agents to adhere glass fibers to a polymer matrix, stabilizing the composite material. They can also be used to couple a bio-inert layer on a titanium implant. Other applications include water repellents, masonry protection, control of graffiti,[6] applying polycrystalline silicon layers on silicon wafers when manufacturing semiconductors, and sealants. Semiconductor industry alone used about 300 metric tons per year of silane in the late 1990s.[3] More recently, a growth in low-cost solar panel manufacturing has lead to substantial consumption of silane for depositing amorphous silicon on glass and other surfaces.
Silane is also used in supersonic combustion ramjets to initiate combustion in the compressed air stream.
Silane and similar compounds containing Si-H-bonds are used as reducing agents in organic and organometallic chemistry.[7]
"Mars sand" exposes regular sand to trimethylhydroxysilane vapors to make the sand waterproof.
Silane may be used to fabricate a super-compressed, superconducting compound.[5]
# Safety and precautions
A number of fatal industrial accidents produced by detonation and combustion of leaked silane in air have been reported.[8][9][10] Dilute silane mixtures with inert gases such as nitrogen or argon are even more likely to ignite when leaked into open air, compared to pure silane: even a 1% mixture of silane in pure nitrogen easily ignites when exposed to air.[11] Unlike methane, silane is also fairly toxic: the lethal concentration in air for rats (LC50) is 0.96% over a 4-hour exposure. In addition, contact with eyes may form silicic acid with resultant irritation.[12] | https://www.wikidoc.org/index.php/Silane | |
10fa53fdae8e95e0b53e52bfa964018a5c9f249a | wikidoc | Slides | Slides
# Step 1: Use WikiDoc's Slide Template to Prepare Your Slides
All WikiDoc slides follow the same template. Click on the image below to download the slides template.
# Step 2: Upload the Slides on the WikiDoc Server
Slides can be inserted into a WikiDoc page only if they have been uploaded onto the WikiDoc server (the computer that serves up all the pages you view). If the slides you want to insert are not yet on the server, you can add them (a process called "uploading" them) onto the server. To reach the upload page, you can either click Special:Upload| here] or search WikiDoc for Special:Upload. This page has all of the details for adding or uploading the image to the server.
On the Upload file page you will see the following two boxes:
Where it says "Source file name:" you will click on the gray button "browse" and find the file on your computer's hard drive that you want to add to WikiDoc.
Where it says "Destination file name:" you will simply type in the name you want the slideset to have on WikiDoc. Please use a name that is descriptive of the slideset so that it will be found and cataloged by search engines. This point must be stressed, name the file similar to a search criteria that you would use to find that image using a search engine's image function.
Next, click on the button that says "Upload file".
Next, the uploaded slideset will appear. Hint: copy the name of the file so that you can insert it on the WikiDoc page you would like.
Once you or anyone else have added a slideset the server, that slideset can then be inserted on an any number of pages.
You can find the file names of the slides, images, videos and other media that have been uploaded to WikiDoc on the File list. You will need to know the file name of the slideset to insert the image.
# Step 3: Placing the Slide Set into a Chapter
Now that you have uploaded your slideset to the server, you will be able to place a link to download the slideset in any chapter. It is generally best to place the slideset at above the content to which it pertains and in such a manner that it is obvious to the viewer that it is available to them to download.
To create the link to a slideset you will create an internal link to the file, just as you would link to another page on WikiDoc using ]. An example can be found below. | Slides
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Step 1: Use WikiDoc's Slide Template to Prepare Your Slides
All WikiDoc slides follow the same template. Click on the image below to download the slides template.
# Step 2: Upload the Slides on the WikiDoc Server
Slides can be inserted into a WikiDoc page only if they have been uploaded onto the WikiDoc server (the computer that serves up all the pages you view). If the slides you want to insert are not yet on the server, you can add them (a process called "uploading" them) onto the server. To reach the upload page, you can either click Special:Upload| here] or search WikiDoc for Special:Upload. This page has all of the details for adding or uploading the image to the server.
On the Upload file page you will see the following two boxes:
Where it says "Source file name:" you will click on the gray button "browse" and find the file on your computer's hard drive that you want to add to WikiDoc.
Where it says "Destination file name:" you will simply type in the name you want the slideset to have on WikiDoc. Please use a name that is descriptive of the slideset so that it will be found and cataloged by search engines. This point must be stressed, name the file similar to a search criteria that you would use to find that image using a search engine's image function.
Next, click on the button that says "Upload file".
Next, the uploaded slideset will appear. Hint: copy the name of the file so that you can insert it on the WikiDoc page you would like.
Once you or anyone else have added a slideset the server, that slideset can then be inserted on an any number of pages.
You can find the file names of the slides, images, videos and other media that have been uploaded to WikiDoc on the File list. You will need to know the file name of the slideset to insert the image.
# Step 3: Placing the Slide Set into a Chapter
Now that you have uploaded your slideset to the server, you will be able to place a link to download the slideset in any chapter. It is generally best to place the slideset at above the content to which it pertains and in such a manner that it is obvious to the viewer that it is available to them to download.
To create the link to a slideset you will create an internal link to the file, just as you would link to another page on WikiDoc using [[media:filename.ppt|Name you want to appear]]. An example can be found below. | https://www.wikidoc.org/index.php/Slides | |
9d42876336df5edc215789aca5f78095667e027c | wikidoc | SnoRNA | SnoRNA
Small nucleolar RNAs (snoRNAs) are a class of small RNA molecules that guide chemical modifications (methylation or pseudouridylation) of ribosomal RNAs (rRNAs) and other RNA genes (tRNAs and other small nuclear RNAs (snRNAs)). They are classified under snRNA in MeSH. SnoRNAs are commonly referred to as guide RNAs but should not be confused with the guide RNAs (gRNA) that direct RNA editing in trypanosomes.
"Small nucleolar RNAs (snoRNAs) are 60–300-nucleotide-long RNAs located in the nucleolus or in Cajal bodies. They constitute one of the most abundant classes of ncRNAs . Predominantly intronic, 300 different snoRNA sequences are located in the human genome. They are classified into two categories, those containing boxes C and D; and, those containing boxes H and ACA. snoRNAs are generated after splicing, debranching, and trimming of mRNA introns. Subsequently, mature snoRNAs associate with proteins to form small nucleolar ribonucleoproteins (snoRNPs). These complexes are exported into the nucleolus to participate in rRNA processing ."
Tiny "RNAs with a modal length of 18 nt map within -60 to +120 nt of transcription start sites (TSSs) in human, chicken and Drosophila. These transcription initiation RNAs (tiRNAs) are derived from sequences on the same strand as the TSS and are preferentially associated with G+C-rich promoters. The 5' ends of tiRNAs show peak density 10-30 nt downstream of TSSs, indicating that they are processed. tiRNAs are generally, although not exclusively, associated with highly expressed transcripts and sites of RNA polymerase II binding."
"With exception of U3 all box C/D snoRNAs presented in this study are intron-encoded, as it is the general pathway for the biogenesis of this class of snoRNAs (22)."
"Box C/D snoRNAs contain conserved Box C (UGAUGA) and Box D (CUGA) elements located closely to the 5′- and 3′-ends, respectively. Internal copies of these elements are termed Box C′ and Box D′ (20,21)."
Five "principal motif-based classes of D. melanogaster promoters were proposed15, which could be further grouped into three general functional classes16."
"Type I consists of the tissue-specific promoters, which are similar to the low-CpG class in mammals with respect to motif composition, stage of development at which they are expressed and tissue specificity, and they are characterized by a high enrichment for a TATA box at an appropriate distance from an initiator element (Inr element). Type II promoters are associated with ‘housekeeping’ genes and genes that are regulated at the level of individual cells; they have either a DNA recognition element (DRE) or a combination of novel motifs15. Finally, type III promoters have an Inr element only or an Inr element plus a downstream promoter element (DPE). These promoters are preferentially associated with developmentally regulated genes, the expression of which is precisely coordinated across different cells in a tissue or anatomical structure16."
# snoRNA guided modifications
After transcription, nascent rRNA molecules (termed pre-rRNA) are required to undergo a series of processing steps in order to generate the mature rRNA molecule. Prior to cleavage by exo- and endonucleases the pre-rRNA undergoes a complex pattern of nucleoside modifications. These include methylations and pseudouridylations, guided by snoRNAs.
- Methylation is the attachment or substitution of a methyl group onto various substrates. The rRNA of humans contain approximately 115 methyl group modifications. The majority of these are 2'O-ribose-methylations ( where the methyl group is attached to the ribose group) .
- Pseudouridylation is the conversion (isomerisation) of the nucleoside uridine to a different isomeric form pseudouridine(Ψ). Mature human rRNAs contain approximately 95 Ψ modifications.
Each snoRNA molecule acts as a guide for only one (or two) individual modifications in a target RNA. In order to carry out modification, each snoRNA associates with at least four protein molecules in an RNA/protein complex referred to as a small nucleolar ribonucleoprotein (snoRNP). The proteins associated with each RNA depend on the type of snoRNA molecule (see snoRNA guide families below). The snoRNA molecule contains an antisense element (a stretch of 10-20 nucleotides) which are base complementary to the sequence surrounding the base (nucleotide) targeted for modification in the pre-RNA molecule. This enables the snoRNP to recognise and bind to the target RNA. Once the snoRNP has bound to the target site the associated proteins are in the correct physical location to catalyse the chemical modification of the target base.
# snoRNA guide families
"Small nucleolar RNAs (snoRNAs) are noncoding RNAs involved in the processing and modification of ribosomal RNAs. They are grouped in two distinct families, the box C/D family, which catalyzes methylation of 2′-hydroxyls of the pre-rRNA precursor, and the box H/ACA family, which catalyzes the modification of uridines into pseudouridines in various RNAs (reviewed in Refs. and )."
The two different types of rRNA modification (methylation and pseudouridylation) are directed by two different families of snoRNPs. These families of snoRNAs are referred to as antisense C/D box and H/ACA box snoRNAs based on the presence of conserved sequence motifs in the snoRNA. There are exceptions but as a general rule C/D box members guide methylation and H/ACA members guide pseudouridylation. The members of each family may vary in biogenesis, structure and function but each family is classified by the following generalised characteristics. For more detail see review .
## C/D box
C/D box snoRNAs contain two short conserved sequence motifs, C (UGAUGA) and D (CUGA) located near the 5' and 3' ends of the snoRNA respectively. Short regions (~ 5 nucleotides) located upstream of the C box and downstream of the D box are usually base complementary and form a stem-box structure which brings the C and D box motifs into close proximity. This stem-box structure has been shown to be essential for correct snoRNA synthesis and nucleolar localization . Many C/D box snoRNA also contain an additional less well conserved copy of the C and D motifs (referred to as C' and D') located in the central portion of the snoRNA molecule. A conserved region of 10-21 nucleotides upstream of the D box is complementary to the methylation site of the target RNA and enables the snoRNA to form and RNA duplex with the RNA . The nucleotide to be modified in the target RNA is usually located at the 5th position upstream from the D box (or D' box) . Box C/D snoRNAs associate with four evolutionary conserved and essential proteins ( Fibrillarin (Nop1p), Nop56p, Nop58p and Snu13 ) which make up the core C/D box snoRNP .
## H/ACA box
H/ACA box snoRNAs have a common secondary structure consisting of a two hairpins and two single stranded regions termed a hairpin-hinge-hairpin-tail structure . H/ACA snoRNAs also contain conserved sequence motifs known as H box (consensus ANANNA) and the ACA box (ACA). Both motifs are usually located in the single stranded regions of the secondary structure. The H motif is located in the hinge and the ACA motif is located in the tail region, 3 nucleotides from the 3' end of the sequence . The hairpin regions contain internal bulges known as recognition loops in which the antisense guide sequences (bases complementary to the target sequence) are located. This recognition sequence is bipartite (constructed from the two different arms of the loop region) and forms complex pseudo-knots with the target RNA. H/ACA box snoRNAs associate with four evolutionary conserved and essential proteins ( dyskerin (Cbf5p), Gar1p, Nhp2p and Nop10p) which make up the core of the H/ACA box snoRNP .
## Composite H/ACA and C/D box
An unusual guide snoRNA U85 was identified that functions in both 2'-O-ribose methylation and pseudouridylation of small nuclear RNA (snRNA) U5 . This composite snoRNA contains both C/D and H/ACA box domains and associates with the proteins specific to each class of snoRNA (fibrillaring and Gar1p respectively. More composite snoRNAs have now been characterised .
These composite snoRNAs have been found to accumulate in a subnuclear organelle called the Cajal body and are referred to as Cajal body specific RNAs. This is in contrast to the majority of C/D box or H/ACA box snoRNAs which localise to the nucleolus. These Cajal body specific RNAs and are proposed to be involved in the modification of RNA polymerase II transcribed spliceosomal RNAs U1, U2, U4, U5 and U12. Not all snoRNAs that have been localised to Cajal bodies are composite C/D and H/ACA box snoRNAs.
# snoRNA targets
The targets for newly identified snoRNAs are predicted on the basis of sequence complementarity between putative target RNAs and the antisense elements or recognition loops in the snoRNA sequence. However, there are an increasing number of 'orphan' guides without any known RNA targets, which suggests that there might be more proteins or transcripts involved in rRNA than previously and/or that some snoRNAs have different functions not concerning rRNA.
# Target modifications
The precise effect of the methylation and pseudouridylation modifications on the function of the mature RNAs is not yet known. The modifications do not appear to be essential but are known to subtly enhance the RNA folding and interaction with ribosomal proteins. In support of their importance, target site modifications are exclusively located within conserved and functionally important domains of the mature RNA and are commonly conserved amongst distant eukaryotes .
- 2'-O-methylated ribose causes an increase in the 3'-endo conformation
- Pseudouridine (psi/Ψ) adds another option for H-bonding.
- Heavily methylated RNA is protected from hydrolysis. rRNA acts as a ribozyme by catalyzing its own hydrolysis and splicing.
# Genomic organisation
The majority of snoRNA genes are encoded in the introns of proteins involved in ribosome synthesis or translation, and are synthesized by RNA polymerase II, but can also be transcribed from their own promoters by RNA polymerase II or III.
# Other functions of snoRNA
Recently, it has been found that snoRNAs can have functions not related to rRNA. One such function is the regulation of alternative splicing of the trans gene transcript, which is done by the snoRNA HBII-52. | SnoRNA
Associate Editor(s)-in-Chief: Henry A. Hoff
Small nucleolar RNAs (snoRNAs) are a class of small RNA molecules that guide chemical modifications (methylation or pseudouridylation) of ribosomal RNAs (rRNAs) and other RNA genes (tRNAs and other small nuclear RNAs (snRNAs)). They are classified under snRNA in MeSH. SnoRNAs are commonly referred to as guide RNAs but should not be confused with the guide RNAs (gRNA) that direct RNA editing in trypanosomes.
"Small nucleolar RNAs (snoRNAs) are 60–300-nucleotide-long RNAs located in the nucleolus or in Cajal bodies. They constitute one of the most abundant classes of ncRNAs [9]. Predominantly intronic, 300 different snoRNA sequences are located in the human genome. They are classified into two categories, those containing boxes C and D; and, those containing boxes H and ACA. snoRNAs are generated after splicing, debranching, and trimming of mRNA introns. Subsequently, mature snoRNAs associate with proteins to form small nucleolar ribonucleoproteins (snoRNPs). These complexes are exported into the nucleolus to participate in rRNA processing [5]."[1]
Tiny "RNAs with a modal length of 18 nt [...] map within -60 to +120 nt of transcription start sites (TSSs) in human, chicken and Drosophila. These transcription initiation RNAs (tiRNAs) are derived from sequences on the same strand as the TSS and are preferentially associated with G+C-rich promoters. The 5' ends of tiRNAs show peak density 10-30 nt downstream of TSSs, indicating that they are processed. tiRNAs are generally, although not exclusively, associated with highly expressed transcripts and sites of RNA polymerase II binding."[2]
"With exception of U3 all box C/D snoRNAs presented in this study are intron-encoded, as it is the general pathway for the biogenesis of this class of snoRNAs (22)."[3]
"Box C/D snoRNAs [...] contain conserved Box C (UGAUGA) and Box D (CUGA) elements located closely to the 5′- and 3′-ends, respectively. Internal copies of these elements are termed Box C′ and Box D′ (20,21)."[3]
Five "principal motif-based classes of D. melanogaster promoters were proposed15, which could be further grouped into three general functional classes16."[4]
"Type I consists of the tissue-specific promoters, which are similar to the low-CpG class in mammals with respect to motif composition, stage of development at which they are expressed and tissue specificity, and they are characterized by a high enrichment for a TATA box at an appropriate distance from an initiator element (Inr element). Type II promoters are associated with ‘housekeeping’ genes and genes that are regulated at the level of individual cells; they have either a DNA recognition element (DRE) or a combination of novel motifs15. Finally, type III promoters have an Inr element only or an Inr element plus a downstream promoter element (DPE). These promoters are preferentially associated with developmentally regulated genes, the expression of which is precisely coordinated across different cells in a tissue or anatomical structure16."[4]
# snoRNA guided modifications
After transcription, nascent rRNA molecules (termed pre-rRNA) are required to undergo a series of processing steps in order to generate the mature rRNA molecule. Prior to cleavage by exo- and endonucleases the pre-rRNA undergoes a complex pattern of nucleoside modifications. These include methylations and pseudouridylations, guided by snoRNAs.
- Methylation is the attachment or substitution of a methyl group onto various substrates. The rRNA of humans contain approximately 115 methyl group modifications. The majority of these are 2'O-ribose-methylations ( where the methyl group is attached to the ribose group) [5].
- Pseudouridylation is the conversion (isomerisation) of the nucleoside uridine to a different isomeric form pseudouridine(Ψ). Mature human rRNAs contain approximately 95 Ψ modifications[5].
Each snoRNA molecule acts as a guide for only one (or two) individual modifications in a target RNA. In order to carry out modification, each snoRNA associates with at least four protein molecules in an RNA/protein complex referred to as a small nucleolar ribonucleoprotein (snoRNP). The proteins associated with each RNA depend on the type of snoRNA molecule (see snoRNA guide families below). The snoRNA molecule contains an antisense element (a stretch of 10-20 nucleotides) which are base complementary to the sequence surrounding the base (nucleotide) targeted for modification in the pre-RNA molecule. This enables the snoRNP to recognise and bind to the target RNA. Once the snoRNP has bound to the target site the associated proteins are in the correct physical location to catalyse the chemical modification of the target base.
# snoRNA guide families
"Small nucleolar RNAs (snoRNAs) are noncoding RNAs involved in the processing and modification of ribosomal RNAs. They are grouped in two distinct families, the box C/D family, which catalyzes methylation of 2′-hydroxyls of the pre-rRNA precursor, and the box H/ACA family, which catalyzes the modification of uridines into pseudouridines in various RNAs (reviewed in Refs. [24] and [40])."[6]
The two different types of rRNA modification (methylation and pseudouridylation) are directed by two different families of snoRNPs. These families of snoRNAs are referred to as antisense C/D box and H/ACA box snoRNAs based on the presence of conserved sequence motifs in the snoRNA. There are exceptions but as a general rule C/D box members guide methylation and H/ACA members guide pseudouridylation. The members of each family may vary in biogenesis, structure and function but each family is classified by the following generalised characteristics. For more detail see review [7].
## C/D box
C/D box snoRNAs contain two short conserved sequence motifs, C (UGAUGA) and D (CUGA) located near the 5' and 3' ends of the snoRNA respectively. Short regions (~ 5 nucleotides) located upstream of the C box and downstream of the D box are usually base complementary and form a stem-box structure which brings the C and D box motifs into close proximity. This stem-box structure has been shown to be essential for correct snoRNA synthesis and nucleolar localization [8]. Many C/D box snoRNA also contain an additional less well conserved copy of the C and D motifs (referred to as C' and D') located in the central portion of the snoRNA molecule. A conserved region of 10-21 nucleotides upstream of the D box is complementary to the methylation site of the target RNA and enables the snoRNA to form and RNA duplex with the RNA [9]. The nucleotide to be modified in the target RNA is usually located at the 5th position upstream from the D box (or D' box) [10] [11]. Box C/D snoRNAs associate with four evolutionary conserved and essential proteins ( Fibrillarin (Nop1p), Nop56p, Nop58p and Snu13 ) which make up the core C/D box snoRNP [7].
## H/ACA box
H/ACA box snoRNAs have a common secondary structure consisting of a two hairpins and two single stranded regions termed a hairpin-hinge-hairpin-tail structure [7]. H/ACA snoRNAs also contain conserved sequence motifs known as H box (consensus ANANNA) and the ACA box (ACA). Both motifs are usually located in the single stranded regions of the secondary structure. The H motif is located in the hinge and the ACA motif is located in the tail region, 3 nucleotides from the 3' end of the sequence [12]. The hairpin regions contain internal bulges known as recognition loops in which the antisense guide sequences (bases complementary to the target sequence) are located. This recognition sequence is bipartite (constructed from the two different arms of the loop region) and forms complex pseudo-knots with the target RNA. H/ACA box snoRNAs associate with four evolutionary conserved and essential proteins ( dyskerin (Cbf5p), Gar1p, Nhp2p and Nop10p) which make up the core of the H/ACA box snoRNP [7].
## Composite H/ACA and C/D box
An unusual guide snoRNA U85 was identified that functions in both 2'-O-ribose methylation and pseudouridylation of small nuclear RNA (snRNA) U5 [13]. This composite snoRNA contains both C/D and H/ACA box domains and associates with the proteins specific to each class of snoRNA (fibrillaring and Gar1p respectively. More composite snoRNAs have now been characterised [14].
These composite snoRNAs have been found to accumulate in a subnuclear organelle called the Cajal body and are referred to as Cajal body specific RNAs. This is in contrast to the majority of C/D box or H/ACA box snoRNAs which localise to the nucleolus. These Cajal body specific RNAs and are proposed to be involved in the modification of RNA polymerase II transcribed spliceosomal RNAs U1, U2, U4, U5 and U12[14]. Not all snoRNAs that have been localised to Cajal bodies are composite C/D and H/ACA box snoRNAs.
# snoRNA targets
The targets for newly identified snoRNAs are predicted on the basis of sequence complementarity between putative target RNAs and the antisense elements or recognition loops in the snoRNA sequence. However, there are an increasing number of 'orphan' guides without any known RNA targets, which suggests that there might be more proteins or transcripts involved in rRNA than previously and/or that some snoRNAs have different functions not concerning rRNA.[15]
# Target modifications
The precise effect of the methylation and pseudouridylation modifications on the function of the mature RNAs is not yet known. The modifications do not appear to be essential but are known to subtly enhance the RNA folding and interaction with ribosomal proteins. In support of their importance, target site modifications are exclusively located within conserved and functionally important domains of the mature RNA and are commonly conserved amongst distant eukaryotes [7].
- 2'-O-methylated ribose causes an increase in the 3'-endo conformation
- Pseudouridine (psi/Ψ) adds another option for H-bonding.
- Heavily methylated RNA is protected from hydrolysis. rRNA acts as a ribozyme by catalyzing its own hydrolysis and splicing.
# Genomic organisation
The majority of snoRNA genes are encoded in the introns of proteins involved in ribosome synthesis or translation, and are synthesized by RNA polymerase II, but can also be transcribed from their own promoters by RNA polymerase II or III.
# Other functions of snoRNA
Recently, it has been found that snoRNAs can have functions not related to rRNA. One such function is the regulation of alternative splicing of the trans gene transcript, which is done by the snoRNA HBII-52.[16] | https://www.wikidoc.org/index.php/Small_nucleolar_RNA | |
dec99b42c8457fd836c92ee133b4de8464cad647 | wikidoc | Smegma | Smegma
Smegma, a transliteration of the Greek word σμήγμα for sebum, is a combination of exfoliated (shed) epithelial cells, transudated skin oils, and moisture, and can accumulate under the foreskin of males and within the vulva of females. It has a characteristic strong odor. Smegma is common to all mammals, male and female. Mycobacterium smegmatis is the characteristic bacterium involved in smegma production, and is generally thought to form smegma from epidermal secretions.
# Mammalian smegma
In healthy animals, smegma helps clean and lubricate the genitals. In veterinary medicine, analysis of this smegma is sometimes used for detection of urinary infections, such as trichomoniasis. Some have recommended periodic cleaning of male genitals to improve the health of the animal.
## Human smegma
Both males and females produce smegma. In males smegma is produced and accumulates under the foreskin of uncircumcised individuals; in females it collects around the clitoris and in the folds of the labia minora.
Smegma is noticeable as a smooth or moist texture until it is allowed to accumulate, when it takes on its characteristic texture and appearance described in many texts as "cheesy". Since smegma tends to accumulate under the foreskin in males, its presence is less common and less noticeable in circumcised males.
The subpreputial moisture keeps the glans moist and may lubricate the movement of the foreskin. However, if allowed to accumulate and decay in the foreskin cavity it can provide an ideal medium for potentially pathogenic bacteria to colonize; current medical opinion is that allowing smegma to accumulate freely is unhealthy. Accumulation of smegma can cause or aggravate a variety of irritations known as balanitis. Early medical studies such as those by Plaut (1947) and Heins et al (1958) claimed that smegma accumulation led to the development of penile cancer, but the American Cancer Society states that more recent studies have failed to support this.
Preventing accumulation is best done by rinsing the area with warm water. In females, the hood of the clitoris can be gently pulled back to wash away accumulated smegma. Some argue that soap is best avoided because it depletes natural skin oils and may cause non-specific dermatitis. Noticeably unpleasant odors can be an indicator of a potentially serious medical problem, or a need to gently wash away excess with water. Deodorant sprays or washes may cause thrush or thrush like conditions—washing using warm water only is recommended by health professionals.
Smegma has become part of a campaign being waged by a small but vocal anti-circumcision movement, with the movement citing the potential usefulness of smegma, which is generally lost following circumcision.
Medical opinion is split on the whether this may be true or not.
It is one of the few English words referring to aspects of human genitalia that are ultimately of Greek form and origin, rather than Latin. | Smegma
Smegma, a transliteration of the Greek word σμήγμα for sebum, is a combination of exfoliated (shed) epithelial cells, transudated skin oils, and moisture, and can accumulate under the foreskin of males and within the vulva of females. It has a characteristic strong odor. Smegma is common to all mammals, male and female. Mycobacterium smegmatis is the characteristic bacterium involved in smegma production, and is generally thought to form smegma from epidermal secretions.
# Mammalian smegma
In healthy animals, smegma helps clean and lubricate the genitals. In veterinary medicine, analysis of this smegma is sometimes used for detection of urinary infections, such as trichomoniasis. Some have recommended periodic cleaning of male genitals to improve the health of the animal.[1]
## Human smegma
Both males and females produce smegma. In males smegma is produced and accumulates under the foreskin of uncircumcised individuals; in females it collects around the clitoris and in the folds of the labia minora.
Smegma is noticeable as a smooth or moist texture until it is allowed to accumulate, when it takes on its characteristic texture and appearance described in many texts as "cheesy". Since smegma tends to accumulate under the foreskin in males, its presence is less common and less noticeable in circumcised males.[2]
The subpreputial moisture keeps the glans moist and may lubricate the movement of the foreskin. However, if allowed to accumulate and decay in the foreskin cavity it can provide an ideal medium for potentially pathogenic bacteria to colonize;[3] current medical opinion is that allowing smegma to accumulate freely is unhealthy. Accumulation of smegma can cause or aggravate a variety of irritations known as balanitis. Early medical studies such as those by Plaut (1947) and Heins et al (1958)[4] claimed that smegma accumulation led to the development of penile cancer, but the American Cancer Society states that more recent studies have failed to support this.[5]
Preventing accumulation is best done by rinsing the area with warm water. In females, the hood of the clitoris can be gently pulled back to wash away accumulated smegma. Some argue that soap is best avoided because it depletes natural skin oils and may cause non-specific dermatitis.[6] Noticeably unpleasant odors can be an indicator of a potentially serious medical problem, or a need to gently wash away excess with water. Deodorant sprays or washes may cause thrush or thrush like conditions—washing using warm water only is recommended by health professionals.[citation needed]
Smegma has become part of a campaign being waged by a small but vocal anti-circumcision movement, with the movement citing the potential usefulness of smegma, which is generally lost following circumcision.
Medical opinion is split on the whether this may be true or not.[citation needed]
It is one of the few English words referring to aspects of human genitalia that are ultimately of Greek form and origin, rather than Latin. | https://www.wikidoc.org/index.php/Smegma | |
bfd8b950d65b7634d70dc322f4316d8fe4be68ed | wikidoc | Sneeze | Sneeze
Synonyms and keywords: Photic sneeze reflex; Peroutka sneeze
# Overview
A sneeze is a semi-autonomous, convulsive expulsion of air from the lungs.
Sneezing occurs when a particle (or sufficient particles) passes through the nasal hairs and reaches the nasal mucosa. This triggers the production of histamines, which reach the nerve cells in the nose, which then send a signal to the brain to initiate the sneeze. The brain relates the initial signal and creates a large opening of the nasal cavity. In certain individuals, sneezing can also be caused by exposure to bright light. This is called the photic sneeze reflex.
In recent years it has been shown that stifling or holding back sneezes can cause damage to the sinuses as well as the inner ear. This is due to the back flow of air pressure. The symptoms of this can include tinnitus, or reduced high frequency hearing, and in extreme cases, rupturing of the ear drum.
Sneezes spread disease by producing infectious droplets that are 0.5 to 5 µm in diameter. About 40,000 such droplets can be produced by a single sneeze.
# Historical Perspective
In 410 BC the Athenian general Xenophon gave a dramatic oration exhorting his fellow soldiers to follow him to liberty or to death against the Persians. He spoke for an hour motivating his army and assuring them a safe return to Athens until a soldier underscored his conclusion with a sneeze. Thinking that this sneeze was a favorable sign from the gods, the soldiers bowed before Xenophon and followed his command. Another divine moment of sneezing for the Greeks occurs in the story of Odysseus. Odysseus returns home disguised as a beggar and talks with his waiting wife Penelope. She says to Odysseus, not knowing to whom she speaks, that he will return safely to challenge her suitors. At that moment their son sneezes loudly and Penelope laughs with joy, reassured that it is a sign from the gods.
According to popular belief, especially in the Japanese culture, a sneeze without an obvious cause is a sign that someone is talking about you.
## Onomatopoeia
Some common English onomatopoeias for the sneeze sound are "achew!", "atisshoo" and "achoo". The first syllable corresponds to the sudden intake of air, the second to the sound of the sneeze. In Cypriot Greek, the word is 'apshoo'. (This is also the name of a village, which is the cause of much mirth.) In French, the sound "Atchoum!" is used, and in Japanese, "Hakushou!"
## Traditional responses to a sneeze
In English-speaking countries, it is common for at least one person to say "God bless you" (or more commonly just "Bless you") after someone sneezes. This tradition originates from the Middle Ages, when it was believed that when one sneezed, the heart stops, the soul left the body and could be snatched by evil spirits. Today, it is said mostly in the spirit of good manners and is usually followed by the sneezer saying 'Thank you'. Also, when the Scarlet Fever broke out for the first time, people would often die as a result. People then began saying God bless you, in the hope that they would survive.
In many cultures words referencing health or good health are used instead of "Bless you". The German word "Gesundheit" is occasionally said after a sneeze. In Spanish, one says "Salud," which means "(to your) health"; in Finnish language, "terveydeksi", which also means "to your health"; in Romanian one says "Sănătate!" ("health") or "Noroc!" ("Luck"). In Hebrew לבריאות — labri'ut or livri'ut — for (the) health. In Norway, Sweden and Denmark, one says "prosit", Latin for "may it advantage (you)". The appropriate response in Russian is "будь здоров(а/ы)," which means "be healthy." In Armenia, one says "առողջություն" (aroghjootyoon). In Turkish, "Cok yasa" which means "live long", which in turn is responded with "sen de gor" (you see too) indicating the person wishing them to live long see them live as long. In Arabic (Jordanian dialect) bless you is صَحة (Sahha) which has probably evolved from Sihha صِحة meaning health! Also, one may say Nashweh نشوة which means ecstasy. The response is either thank you (شكرا Shukran) or Tislam/ Taslam (in different accents)تسلم which means 'may you be kept safe'.
In French, after the first sneeze, one says "à tes souhaits!" which means "to your desires". If the same person sneezes again, the second response is "à tes amours!", which means "to your loves."
The practice among Muslims is based on the Prophetic Traditions. Al-Bukhaari (6224) narrated from Abu Hurayrah that the Islamic prophet, Muhammad said: “When one of you sneezes, let him say, ‘Al-hamdu-Lillaah (Praise be to Allaah),’ and let his brother or companion say to him. ‘Yarhamuk Allaah (May Allaah have mercy on you).’ If he says, ‘Yarhamuk-Allaah,’ then let (the sneezer) say, ‘Yahdeekum Allaah wa yuslihu baalakum (May Allaah guide you and rectify your condition).’”
The Dutch usually say "gezondheid" (literally translated means health) or "proost" (which means cheers.
## Causes
- Aztreonam
- Oxymetazoline
# Related Chapters
- Photic sneeze reflex
- Snatiation
- Sneezing fetishism | Sneeze
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: Photic sneeze reflex; Peroutka sneeze
# Overview
A sneeze is a semi-autonomous, convulsive expulsion of air from the lungs.
Sneezing occurs when a particle (or sufficient particles) passes through the nasal hairs and reaches the nasal mucosa. This triggers the production of histamines, which reach the nerve cells in the nose, which then send a signal to the brain to initiate the sneeze. The brain relates the initial signal and creates a large opening of the nasal cavity. In certain individuals, sneezing can also be caused by exposure to bright light. This is called the photic sneeze reflex.
In recent years it has been shown that stifling or holding back sneezes can cause damage to the sinuses as well as the inner ear. This is due to the back flow of air pressure. The symptoms of this can include tinnitus, or reduced high frequency hearing, and in extreme cases, rupturing of the ear drum.
Sneezes spread disease by producing infectious droplets that are 0.5 to 5 µm in diameter. About 40,000 such droplets can be produced by a single sneeze.[1]
# Historical Perspective
In 410 BC the Athenian general Xenophon gave a dramatic oration exhorting his fellow soldiers to follow him to liberty or to death against the Persians. He spoke for an hour motivating his army and assuring them a safe return to Athens until a soldier underscored his conclusion with a sneeze. Thinking that this sneeze was a favorable sign from the gods, the soldiers bowed before Xenophon and followed his command. Another divine moment of sneezing for the Greeks occurs in the story of Odysseus. Odysseus returns home disguised as a beggar and talks with his waiting wife Penelope. She says to Odysseus, not knowing to whom she speaks, that he will return safely to challenge her suitors. At that moment their son sneezes loudly and Penelope laughs with joy, reassured that it is a sign from the gods.
According to popular belief, especially in the Japanese culture, a sneeze without an obvious cause is a sign that someone is talking about you.
## Onomatopoeia
Some common English onomatopoeias for the sneeze sound are "achew!", "atisshoo" and "achoo". The first syllable corresponds to the sudden intake of air, the second to the sound of the sneeze. In Cypriot Greek, the word is 'apshoo'. (This is also the name of a village, which is the cause of much mirth.) In French, the sound "Atchoum!" is used, and in Japanese, "Hakushou!"
## Traditional responses to a sneeze
In English-speaking countries, it is common for at least one person to say "God bless you" (or more commonly just "Bless you") after someone sneezes. This tradition originates from the Middle Ages, when it was believed that when one sneezed, the heart stops, the soul left the body and could be snatched by evil spirits.[citation needed] Today, it is said mostly in the spirit of good manners and is usually followed by the sneezer saying 'Thank you'. Also, when the Scarlet Fever broke out for the first time, people would often die as a result. People then began saying God bless you, in the hope that they would survive.[citation needed]
In many cultures words referencing health or good health are used instead of "Bless you". The German word "Gesundheit" is occasionally said after a sneeze. In Spanish, one says "Salud," which means "(to your) health"; in Finnish language, "terveydeksi", which also means "to your health"; in Romanian one says "Sănătate!" ("health") or "Noroc!" ("Luck"). In Hebrew לבריאות — labri'ut or livri'ut — for (the) health. In Norway, Sweden and Denmark, one says "prosit", Latin for "may it advantage (you)".[2] The appropriate response in Russian is "будь здоров(а/ы)," which means "be healthy." In Armenia, one says "առողջություն" (aroghjootyoon). In Turkish, "Cok yasa" which means "live long", which in turn is responded with "sen de gor" (you see too) indicating the person wishing them to live long see them live as long. In Arabic (Jordanian dialect) bless you is صَحة (Sahha) which has probably evolved from Sihha صِحة meaning health! Also, one may say Nashweh نشوة which means ecstasy. The response is either thank you (شكرا Shukran) or Tislam/ Taslam (in different accents)تسلم which means 'may you be kept safe'.
In French, after the first sneeze, one says "à tes souhaits!" which means "to your desires". If the same person sneezes again, the second response is "à tes amours!", which means "to your loves."
The practice among Muslims is based on the Prophetic Traditions. Al-Bukhaari (6224) narrated from Abu Hurayrah that the Islamic prophet, Muhammad said: “When one of you sneezes, let him say, ‘Al-hamdu-Lillaah (Praise be to Allaah),’ and let his brother or companion say to him. ‘Yarhamuk Allaah (May Allaah have mercy on you).’ If he says, ‘Yarhamuk-Allaah,’ then let (the sneezer) say, ‘Yahdeekum Allaah wa yuslihu baalakum (May Allaah guide you and rectify your condition).’”
The Dutch usually say "gezondheid" (literally translated means health) or "proost" (which means cheers.
## Causes
- Aztreonam
- Oxymetazoline
# Related Chapters
- Photic sneeze reflex
- Snatiation
- Sneezing fetishism | https://www.wikidoc.org/index.php/Sneeze | |
31bf83971a02e3c0d33da39ced58974f75c8e4ce | wikidoc | Sorrel | Sorrel
Common sorrel, also known as spinach dock and either ambada bhaji or gongoora in Indian cuisine, is a perennial herb that is cultivated as a leaf vegetable.
Sorrel is a slender plant about 60 cm high, with roots that run deep into the ground, as well as juicy stems and edible, oblong leaves. The lower leaves are 7 to 15 cm in length, slightly arrow-shaped at the base, with very long petioles. The upper ones are sessile, and frequently become crimson. The leaves are eaten by the larvae of several species of Lepidoptera including blood-vein.
It has whorled spikes of reddish-green flowers, which bloom in June and July, becoming purplish. The stamens and pistils are on different plants; the ripe seeds are brown and shining.
Common sorrel has been cultivated for centuries. The leaves may be puréed in soups and sauces or added to salads and shav; they have a flavor that is similar to kiwifruit or sour wild strawberries. The plant's sharp taste is due to oxalic acid, and so may be contraindicated in people with rheumatic-type complaints, kidney or bladder stones. Sorrel is also a laxative.
In the Caribbean, sorrel typically refers to Jamaican Red Sorrel or Roselle. A popular dark red sorrel beverage has a sweet, spiced flavor. Roselle is also used in tarts and jellies, and the fiber is used by craftspeople.
ca:Agrella
cs:Šťovík kyselý
de:Wiesen-Sauerampfer
eo:Okzalo
gl:Aceda
-s:Хуырхæг
is:Túnsúra
it:Rumex acetosa
hu:Sóska
nl:Veldzuring
fi:Niittysuolaheinä
sv:Ängssyra
uk:Щавель кислий | Sorrel
Common sorrel, also known as spinach dock and either ambada bhaji or gongoora in Indian cuisine, is a perennial herb that is cultivated as a leaf vegetable.
Sorrel is a slender plant about 60 cm high, with roots that run deep into the ground, as well as juicy stems and edible, oblong leaves. The lower leaves are 7 to 15 cm in length, slightly arrow-shaped at the base, with very long petioles. The upper ones are sessile, and frequently become crimson. The leaves are eaten by the larvae of several species of Lepidoptera including blood-vein.
It has whorled spikes of reddish-green flowers, which bloom in June and July, becoming purplish. The stamens and pistils are on different plants; the ripe seeds are brown and shining.
Common sorrel has been cultivated for centuries. The leaves may be puréed in soups and sauces or added to salads and shav; they have a flavor that is similar to kiwifruit or sour wild strawberries. The plant's sharp taste is due to oxalic acid, and so may be contraindicated in people with rheumatic-type complaints, kidney or bladder stones. Sorrel is also a laxative.
In the Caribbean, sorrel typically refers to Jamaican Red Sorrel or Roselle. A popular dark red sorrel beverage has a sweet, spiced flavor. Roselle is also used in tarts and jellies, and the fiber is used by craftspeople.
Template:Herbs & spices
ca:Agrella
cs:Šťovík kyselý
de:Wiesen-Sauerampfer
eo:Okzalo
gl:Aceda
os:Хуырхæг
is:Túnsúra
it:Rumex acetosa
hu:Sóska
nl:Veldzuring
fi:Niittysuolaheinä
sv:Ängssyra
uk:Щавель кислий
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Sorrel | |
9e0261becbf07aef57f39cd459724c566f006a40 | wikidoc | Spleen | Spleen
# Overview
The spleen is an organ located in the abdomen of the human body, where it functions in the destruction of old red blood cells and holding a small reservoir of blood. It is regarded as one of the centers of activity of the reticuloendothelial system (part of the immune system). Until recently, the purpose of the spleen was not known. It is increasingly recognized that its absence leads to a predisposition to certain infections.
# Anatomy
The human spleen is located in the upper left part of the abdomen, behind the stomach and just below the diaphragm. In normal individuals this organ measures about 125 × 75 × 50 mm (5 × 3 × 2 inches) in size, with an average weight of 150 grams (5 oz).
The spleen is the largest organ derived from mesenchyme and lying in the mesentery. It consists of masses of lymphoid tissue of granular appearance located around fine terminal branches of veins and arteries. These vessels are connected by modified capillaries called splenic sinuses.
Approximately 10% of people have one or more accessory spleens. They may form near the hilum of the main spleen, the junction at which the splenic vessels enter and leave the organ.
There are several peritoneal ligaments that support the spleen (to understand their naming it helps to know that "lien" is an alternate root for "spleen")
- gastrolienal ligament (gastrosplenic) - connects stomach to spleen.
- lienorenal ligament (splenorenal) - connects spleen to kidney.
- phrenicocolic ligament - connects left colic flexure to the thoracic diaphragm. The middle connects to the spleen.
Cross sections of the spleen reveal a red soft surface which is divided into two types of pulp which correspond to the two most important functional roles of the spleen, summarized below:
Other functions of the spleen are less prominent, especially in the healthy adult:
- Production of opsonins, properdin, and tuftsin.
- Creation of red blood cells. While the bone marrow is the primary site of hematopoeisis in the adult, up until the fifth month of gestation, the spleen has important hematopoietic functions. After birth, no significant hematopoietic function is left in the spleen except in some hematologic disorders: e.g. myelodysplastic syndrome, hemoglobinopathies.
- Storage of red blood cells and other formed elements. This is only valid for certain mammals, such as dogs and horses. In horses roughly 50% of the red blood cells are stored there. The red blood cells can be released when needed. In humans, however, the spleen does not function as a depository of red blood cells, but instead it stores platelets in case of an emergency . These animals also have large hearts in relation to their body size to accommodate the higher-viscosity blood that results. Some athletes have tried doping themselves with their own stored red blood cells to try to achieve the same effect, but the human heart is not equipped to handle the higher-viscosity blood.
# Disorders
Enlargement of the spleen is known as splenomegaly. It may be caused by sickle cell anemia, sarcoidosis, malaria, bacterial endocarditis, leukemia, pernicious anaemia, Gaucher's disease, leishmaniasis, Hodgkin's disease, Banti's disease, hereditary spherocytosis, cysts, glandular fever (mononucleosis or 'Mono' caused by the Epstein-Barr Virus), and tumours. Primary tumours of the spleen include hemangiomas and hemangiosarcomas. Marked splenomegaly may result in the spleen occupying a large portion of the left side of the abdomen.
The spleen is the largest collection of lymphoid tissue in the body. It is normally palpable in preterm infants, in 30% of normal, full-term neonates, and in 5% to 10% of infants and toddlers. A spleen easily palpable below the costal margin in any child over the age of 3-4 years should be considered abnormal until proven otherwise.
Splenomegaly can result from antigenic stimulation (eg, infection), obstruction of blood flow (eg, portal vein obstruction), underlying functional abnormality (eg, hemolytic anemia), or infiltration (eg, leukemia or storage disease, such as Gaucher's disease). The most common cause of acute splenomegaly in children is viral infection, which is transient and usually moderate. Basic work-up for acute splenomegaly includes a complete blood count with differential, platelet count, and reticulocyte and atypical lymphocyte counts to exclude hemolytic anemia and leukemia. Assessment of IgM antibodies to viral capsid antigen (a rising titer) is indicated to confirm Epstein-Barr virus or cytomegalovirus. Other infections should be excluded if these tests are negative.
# Absence
The absence of a spleen predisposes to some septicaemia infections. Vaccination and antibiotic measures are discussed under asplenia.
- Some people congenitally completely lack a spleen, although this is rare.
- Sickle-cell disease can cause a functional asplenia (or autosplenectomy) by causing infarctions of the spleen during repeated sickle-cell crises.
- It may be removed surgically (known as a splenectomy), but this is rarely performed, as it carries a high risk of infection and other adverse effects. Indications include following abdominal injuries with rupture and hemorrhage of the spleen, or in the treatment of certain blood diseases (Idiopathic thrombocytopenic purpura, hereditary spherocytosis, etc.), certain forms of lymphoma or for the removal of splenic tumours or cysts.
# Etymology and cultural views
The word spleen comes from the Greek splēn. In Latin its name is lien.
In French, spleen refers to a state of pensive sadness or melancholy. It has been popularized by the poet Charles Baudelaire (1821-1867) but was already used before, in particular in the Romantic literature (18th century). The connection between spleen (the organ) and melancholy (the temperament) comes from the humoral medicine of the ancient Greeks. One of the humours (body fluid) was the black bile, secreted by the spleen organ and associated with melancholy. In contrast, the Talmud (tractate Berachoth 61b) refers to the spleen as the organ of laughter, possibly suggesting a link with the humoral view of the organ.
In German, the word "spleen", pronounced as in English, refers to a persisting somewhat eccentric (but not quite lunatic) idea or habit of a person; however the organ is called "Milz", (cognate with Old English milte).
In 19th century England, women in bad humour were said to be afflicted by the spleen, or the vapours of the spleen. In modern English, "to vent one's spleen" means to vent one's anger, e.g. by shouting, and can be applied to both males and females; similarly, the English term "splenetic" is used to describe a person in a foul mood.
In China, the spleen '脾 (pí)' counts as the seat of one's temperament and is thought to influence the individual's willpower. Analogous to "venting one's spleen", "發脾氣" is used as an expression for getting angry, although in the view of Traditional Chinese Medicine, the view of "脾" does not correspond to the anatomical "spleen".
In chiropractic (meric chart) problems with the spleen relate to T8 (eighth thorasic vertebrea), a subluxation at T8 is associated with low energy and/or low immune system function. | Spleen
Template:Infobox Anatomy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
The spleen is an organ located in the abdomen of the human body, where it functions in the destruction of old red blood cells and holding a small reservoir of blood. It is regarded as one of the centers of activity of the reticuloendothelial system (part of the immune system). Until recently, the purpose of the spleen was not known. It is increasingly recognized that its absence leads to a predisposition to certain infections.
# Anatomy
The human spleen is located in the upper left part of the abdomen, behind the stomach and just below the diaphragm. In normal individuals this organ measures about 125 × 75 × 50 mm (5 × 3 × 2 inches) in size, with an average weight of 150 grams (5 oz).
The spleen is the largest organ derived from mesenchyme and lying in the mesentery. It consists of masses of lymphoid tissue of granular appearance located around fine terminal branches of veins and arteries. These vessels are connected by modified capillaries called splenic sinuses.
Approximately 10% of people have one or more accessory spleens. They may form near the hilum of the main spleen, the junction at which the splenic vessels enter and leave the organ.
There are several peritoneal ligaments that support the spleen[1] (to understand their naming it helps to know that "lien" is an alternate root for "spleen")
- gastrolienal ligament (gastrosplenic) - connects stomach to spleen.
- lienorenal ligament (splenorenal) - connects spleen to kidney.
- phrenicocolic ligament - connects left colic flexure to the thoracic diaphragm. The middle connects to the spleen.
Cross sections of the spleen reveal a red soft surface which is divided into two types of pulp which correspond to the two most important functional roles of the spleen, summarized below:[2]
Other functions of the spleen are less prominent, especially in the healthy adult:
- Production of opsonins, properdin, and tuftsin.
- Creation of red blood cells. While the bone marrow is the primary site of hematopoeisis in the adult, up until the fifth month of gestation, the spleen has important hematopoietic functions. After birth, no significant hematopoietic function is left in the spleen except in some hematologic disorders: e.g. myelodysplastic syndrome, hemoglobinopathies.
- Storage of red blood cells and other formed elements. This is only valid for certain mammals, such as dogs and horses. In horses roughly 50% of the red blood cells are stored there. The red blood cells can be released when needed. In humans, however, the spleen does not function as a depository of red blood cells, but instead it stores platelets in case of an emergency .[3] These animals also have large hearts in relation to their body size to accommodate the higher-viscosity blood that results. Some athletes have tried doping themselves with their own stored red blood cells to try to achieve the same effect, but the human heart is not equipped to handle the higher-viscosity blood.
# Disorders
Enlargement of the spleen is known as splenomegaly. It may be caused by sickle cell anemia, sarcoidosis, malaria, bacterial endocarditis, leukemia, pernicious anaemia, Gaucher's disease, leishmaniasis, Hodgkin's disease, Banti's disease, hereditary spherocytosis, cysts, glandular fever (mononucleosis or 'Mono' caused by the Epstein-Barr Virus), and tumours. Primary tumours of the spleen include hemangiomas and hemangiosarcomas. Marked splenomegaly may result in the spleen occupying a large portion of the left side of the abdomen.
The spleen is the largest collection of lymphoid tissue in the body. It is normally palpable in preterm infants, in 30% of normal, full-term neonates, and in 5% to 10% of infants and toddlers. A spleen easily palpable below the costal margin in any child over the age of 3-4 years should be considered abnormal until proven otherwise.
Splenomegaly can result from antigenic stimulation (eg, infection), obstruction of blood flow (eg, portal vein obstruction), underlying functional abnormality (eg, hemolytic anemia), or infiltration (eg, leukemia or storage disease, such as Gaucher's disease). The most common cause of acute splenomegaly in children is viral infection, which is transient and usually moderate. Basic work-up for acute splenomegaly includes a complete blood count with differential, platelet count, and reticulocyte and atypical lymphocyte counts to exclude hemolytic anemia and leukemia. Assessment of IgM antibodies to viral capsid antigen (a rising titer) is indicated to confirm Epstein-Barr virus or cytomegalovirus. Other infections should be excluded if these tests are negative.
# Absence
The absence of a spleen predisposes to some septicaemia infections. Vaccination and antibiotic measures are discussed under asplenia.
- Some people congenitally completely lack a spleen, although this is rare.
- Sickle-cell disease can cause a functional asplenia (or autosplenectomy) by causing infarctions of the spleen during repeated sickle-cell crises.
- It may be removed surgically (known as a splenectomy), but this is rarely performed, as it carries a high risk of infection and other adverse effects. Indications include following abdominal injuries with rupture and hemorrhage of the spleen, or in the treatment of certain blood diseases (Idiopathic thrombocytopenic purpura, hereditary spherocytosis, etc.), certain forms of lymphoma or for the removal of splenic tumours or cysts.
# Etymology and cultural views
The word spleen comes from the Greek splēn. In Latin its name is lien.
In French, spleen refers to a state of pensive sadness or melancholy. It has been popularized by the poet Charles Baudelaire (1821-1867) but was already used before, in particular in the Romantic literature (18th century). The connection between spleen (the organ) and melancholy (the temperament) comes from the humoral medicine of the ancient Greeks. One of the humours (body fluid) was the black bile, secreted by the spleen organ and associated with melancholy. In contrast, the Talmud (tractate Berachoth 61b) refers to the spleen as the organ of laughter, possibly suggesting a link with the humoral view of the organ.
In German, the word "spleen", pronounced as in English, refers to a persisting somewhat eccentric (but not quite lunatic) idea or habit of a person; however the organ is called "Milz", (cognate with Old English milte).
In 19th century England, women in bad humour were said to be afflicted by the spleen, or the vapours of the spleen. In modern English, "to vent one's spleen" means to vent one's anger, e.g. by shouting, and can be applied to both males and females; similarly, the English term "splenetic" is used to describe a person in a foul mood.
In China, the spleen '脾 (pí)' counts as the seat of one's temperament and is thought to influence the individual's willpower. Analogous to "venting one's spleen", "發脾氣" is used as an expression for getting angry, although in the view of Traditional Chinese Medicine, the view of "脾" does not correspond to the anatomical "spleen".
In chiropractic (meric chart) problems with the spleen relate to T8 (eighth thorasic vertebrea), a subluxation at T8 is associated with low energy and/or low immune system function. | https://www.wikidoc.org/index.php/Spleen | |
9593a4ca2884cdcb29df0a2389a9029921c8c867 | wikidoc | Stapes | Stapes
The stapes or stirrup is the stirrup-shaped small bone or ossicle in the
middle ear which attaches the incus to the fenestra ovalis, the "oval window" which is adjacent to the vestibule of the inner ear. It is the smallest and lightest bone in the human body.
The stapes transmits the sound vibrations from the incus to the membrane of the inner ear inside the fenestra ovalis.
In non-mammalian vertebrates, the bone homologous to the stapes is usually called the columella; however, in reptiles, either term may be used.
- The stapes is the smallest bone in the body.
- Stapes.
- It consists of a capitulum (head) which articulates with the incus, a neck, two crura (anterior and posterior) and a footplate.The head neck and crura form the stapedial arch. | Stapes
Template:Infobox Bone
The stapes or stirrup is the stirrup-shaped small bone or ossicle in the
middle ear which attaches the incus to the fenestra ovalis, the "oval window" which is adjacent to the vestibule of the inner ear. It is the smallest and lightest bone in the human body.
The stapes transmits the sound vibrations from the incus to the membrane of the inner ear inside the fenestra ovalis.
In non-mammalian vertebrates, the bone homologous to the stapes is usually called the columella; however, in reptiles, either term may be used.
- The stapes is the smallest bone in the body[1].
- Stapes[2].
- It consists of a capitulum (head) which articulates with the incus, a neck, two crura (anterior and posterior) and a footplate.The head neck and crura form the stapedial arch.[3] | https://www.wikidoc.org/index.php/Stapes | |
01a7cdd437fcad8e1c0a15fe160674de5a11f686 | wikidoc | Starch | Starch
# Overview
Starch (CAS# 9005-25-8, chemical formula (C6H10O5)n,) is a mixture of amylose and amylopectin (usually in 20:80 or 30:70 ratios). These are both complex carbohydrate polymers of glucose (chemical formula of glucose C6H12O6), making starch a glucose polymer as well, as seen by the chemical formula for starch, regardless of the ratio of amylose:amylopectin.
# Starch in Food
In terms of human nutrition, starch is by far the most consumed polysaccharides in the human diet. It constitutes more than half of the carbohydrates even in many affluent diets, and much more in poorer diets. Traditional staple foods such as cereals, roots and tubers are the main source of dietary starch.
Starch (in particular cornstarch) is used in cooking for thickening foods such as sauce. In industry, it is used in the manufacturing of adhesives, paper, textiles and as a mold in the manufacture of sweets such as wine gums and jelly beans. It is a white powder, and depending on the source, may be tasteless and odourless.
Starch is often found in the fruit, seeds, rhizomes or tubers of plants and is what gives us energy when we eat these. The major resources for starch production and consumption worldwide are rice, wheat, corn, and potatoes. Cooked foods containing starches include boiled rice, various forms of bread and noodles (including pasta).
As an additive for food processing, arrowroot and tapioca are commonly used as well. Commonly used starches around the world are: arracacha, buckwheat, banana, barley, cassava, kudzu, oca, sago, sorghum, sweet potato, taro and yams. Edible beans, such as favas, lentils and peas, are also rich in starch.
When a starch is pre-cooked, it can then be used to thicken cold foods. This is referred to as a pregelatinized starch. Otherwise starch requires heat to thicken, or "gelatinize." The actual temperature depends on the type of starch.
A modified food starch undergoes one or more chemical modifications that allow it to function properly under high heat and/or shear frequently encountered during food processing. Food starches are typically used as thickeners and stabilizers in foods such as puddings, custards, soups, sauces, gravies, pie fillings, and salad dressings, but have many other uses.
Resistant starch is starch that escapes digestion in the small intestine of healthy individuals.
Plants use starch as a way to store excess glucose, and thus also use starch as food during mitochondrial oxidative phosphorylation.
# Non-food applications
Papermaking is the largest non-food application for starches globally, consuming millions of metric tons annually. In a typical sheet of copy paper for instance, the starch content may be as high as 8%. Both chemically modified and unmodified starches are used in papermaking. In the wet part of the papermaking process, generally called the “wet-end”, starches that have been chemically modified to contain a cationic or positive charge bound to the starch polymer, and are utilized to associate with the anionic or negatively charged paper fibers and inorganic fillers. These cationic starches impart the necessary strength properties for the paper web to be formed in the papermaking process (wet strength), and to provide strength to the final paper sheet (dry strength).
In the dry end of the papermaking process the paper web is rewetted with a solution of starch paste that has been chemically, or enzymatically depolymerized. The starch paste solutions are applied to the paper web by means of various mechanical presses (size press). The dry end starches impart additional strength to the paper web and additionally provide water hold out or “size” for superior printing properties.
Corrugating glues are the next largest consumer of non-food starches globally. These glues are used in the production of corrugated fiberboard (sometimes called corrugated cardboard), and generally contain a mixture of chemically modified and unmodified starches that have been partially gelatinized to form an opaque paste. This paste is applied to the flute tips of the interior fluted paper to glue the fluted paper to the outside paper in the construction of cardboard boxes. This is then dried under high heat, which provides the box board strength and rigidity.
Another large non-food starch application is in the construction industry where starch is used in the or wall board manufacturing process. Chemically modified or unmodified starches are added to the rock mud containing primarily gypsum. Top and bottom heavyweight sheets of paper are applied to the mud formulation and the process is allowed to heat and cure to form the eventual rigid wall board. The starches act as a glue for the cured gypsum rock with the paper covering and also provide rigidity to the board.
Clothing starch or laundry starch is a liquid that is prepared by mixing a vegetable starch in water (earlier preparations also had to be boiled), and is used in the laundering of clothes. Starch was widely used in Europe in the 16th and 17th centuries to stiffen the wide collars and ruffs of fine linen which surrounded the necks of the well-to-do. During the 19th century and early 20th century, it was stylish to stiffen the collars and sleeves of men's shirts and the ruffles of girls' petticoats by applying starch to them as the clean clothes were being ironed.
Aside from the smooth, crisp edges it gave to clothing, it served practical purposes as well. Dirt and sweat from a person's neck and wrists would stick to the starch rather than fibers of the clothing, and would easily wash away along with the starch. After each laundering, the starch would be reapplied.
Starch is also used to make some packing peanuts, and some dropped ceiling tiles.
Printing industry - in the printing industry food grade starch is used in the manufacture of anti-set-off spray powder used to separate printed sheets of paper to avoid wet ink being set off. Starch is also used in the manufacture of glues for book-binding.
Hydrogen production - Starch can be used to produce Hydrogen.
# Use as a mold
Gummed sweets such as jelly beans and wine gums are not manufactured using a mold in the conventional sense. A tray is filled with starch and leveled. A positive mold is then pressed into the starch leaving an impression of 1000 or so jelly beans. The mix is then poured into the impressions and then put into a stove to set. This method greatly reduces the number of molds that must be manufactured.
# Tests
Starch solution is used to test for iodine. A blue-black color indicates the presence of iodine in the starch solution. It is thought that the iodine fits inside the coils of amylose. A 0.3% w/w solution is the standard concentration for a dilute starch indicator solution. It is made by adding 4 grams of soluble starch to 1 litre of heated water; the solution is cooled before use (starch-iodine complex becomes unstable at temperatures above 35 °C). This complex is often used in redox titrations: in presence of an oxidizing agent the solution turns blue, in the presence of reducing agent, the blue color disappears because triiodide (I3−) ions break up into three iodide ions, disassembling the complex.
Under the microscope, starch grains show a distinctive Maltese cross effect (also known as 'extinction cross' and birefringence) under polarized light.
# Starch derivatives
Starch can be hydrolyzed into simpler carbohydrates by acids, various enzymes, or a combination of the two. The extent of conversion is typically quantified by dextrose equivalent (DE), which is roughly the fraction of the glycoside bonds in starch that have been broken. Food products made in this way include:
- Maltodextrin, a lightly hydrolyzed (DE 10–20) starch product used as a bland-tasting filler and thickener.
- Various corn syrups (DE 30–70), viscous solutions used as sweeteners and thickeners in many kinds of processed foods.
- Dextrose (DE 100), commercial glucose, prepared by the complete hydrolysis of starch.
- High fructose syrup, made by treating dextrose solutions to the enzyme glucose isomerase, until a substantial fraction of the glucose has been converted to fructose. In the United States, high fructose corn syrup is the principal sweetener used in sweetened beverages because fructose tastes sweeter than glucose, and less sweetener may be used. | Starch
# Overview
Starch (CAS# 9005-25-8, chemical formula (C6H10O5)n,[1]) is a mixture of amylose and amylopectin (usually in 20:80 or 30:70 ratios). These are both complex carbohydrate polymers of glucose (chemical formula of glucose C6H12O6), making starch a glucose polymer as well, as seen by the chemical formula for starch, regardless of the ratio of amylose:amylopectin.
# Starch in Food
In terms of human nutrition, starch is by far the most consumed polysaccharides in the human diet. It constitutes more than half of the carbohydrates even in many affluent diets, and much more in poorer diets. Traditional staple foods such as cereals, roots and tubers are the main source of dietary starch.
Starch (in particular cornstarch) is used in cooking for thickening foods such as sauce. In industry, it is used in the manufacturing of adhesives, paper, textiles and as a mold in the manufacture of sweets such as wine gums and jelly beans. It is a white powder, and depending on the source, may be tasteless and odourless.
Starch is often found in the fruit, seeds, rhizomes or tubers of plants and is what gives us energy when we eat these. The major resources for starch production and consumption worldwide are rice, wheat, corn, and potatoes. Cooked foods containing starches include boiled rice, various forms of bread and noodles (including pasta).
As an additive for food processing, arrowroot and tapioca are commonly used as well. Commonly used starches around the world are: arracacha, buckwheat, banana, barley, cassava, kudzu, oca, sago, sorghum, sweet potato, taro and yams. Edible beans, such as favas, lentils and peas, are also rich in starch.
When a starch is pre-cooked, it can then be used to thicken cold foods. This is referred to as a pregelatinized starch. Otherwise starch requires heat to thicken, or "gelatinize." The actual temperature depends on the type of starch.
A modified food starch undergoes one or more chemical modifications that allow it to function properly under high heat and/or shear frequently encountered during food processing. Food starches are typically used as thickeners and stabilizers in foods such as puddings, custards, soups, sauces, gravies, pie fillings, and salad dressings, but have many other uses.
Resistant starch is starch that escapes digestion in the small intestine of healthy individuals.
Plants use starch as a way to store excess glucose, and thus also use starch as food during mitochondrial oxidative phosphorylation.
# Non-food applications
Papermaking is the largest non-food application for starches globally, consuming millions of metric tons annually. In a typical sheet of copy paper for instance, the starch content may be as high as 8%. Both chemically modified and unmodified starches are used in papermaking. In the wet part of the papermaking process, generally called the “wet-end”, starches that have been chemically modified to contain a cationic or positive charge bound to the starch polymer, and are utilized to associate with the anionic or negatively charged paper fibers and inorganic fillers. These cationic starches impart the necessary strength properties for the paper web to be formed in the papermaking process (wet strength), and to provide strength to the final paper sheet (dry strength).
In the dry end of the papermaking process the paper web is rewetted with a solution of starch paste that has been chemically, or enzymatically depolymerized. The starch paste solutions are applied to the paper web by means of various mechanical presses (size press). The dry end starches impart additional strength to the paper web and additionally provide water hold out or “size” for superior printing properties.
Corrugating glues are the next largest consumer of non-food starches globally. These glues are used in the production of corrugated fiberboard (sometimes called corrugated cardboard), and generally contain a mixture of chemically modified and unmodified starches that have been partially gelatinized to form an opaque paste. This paste is applied to the flute tips of the interior fluted paper to glue the fluted paper to the outside paper in the construction of cardboard boxes. This is then dried under high heat, which provides the box board strength and rigidity.
Another large non-food starch application is in the construction industry where starch is used in the or wall board manufacturing process. Chemically modified or unmodified starches are added to the rock mud containing primarily gypsum. Top and bottom heavyweight sheets of paper are applied to the mud formulation and the process is allowed to heat and cure to form the eventual rigid wall board. The starches act as a glue for the cured gypsum rock with the paper covering and also provide rigidity to the board.
Clothing starch or laundry starch is a liquid that is prepared by mixing a vegetable starch in water (earlier preparations also had to be boiled), and is used in the laundering of clothes. Starch was widely used in Europe in the 16th and 17th centuries to stiffen the wide collars and ruffs of fine linen which surrounded the necks of the well-to-do. During the 19th century and early 20th century, it was stylish to stiffen the collars and sleeves of men's shirts and the ruffles of girls' petticoats by applying starch to them as the clean clothes were being ironed.
Aside from the smooth, crisp edges it gave to clothing, it served practical purposes as well. Dirt and sweat from a person's neck and wrists would stick to the starch rather than fibers of the clothing, and would easily wash away along with the starch. After each laundering, the starch would be reapplied.
Starch is also used to make some packing peanuts, and some dropped ceiling tiles.
Printing industry - in the printing industry food grade starch[2] is used in the manufacture of anti-set-off spray powder used to separate printed sheets of paper to avoid wet ink being set off. Starch is also used in the manufacture of glues[3] for book-binding.
Hydrogen production - Starch can be used to produce Hydrogen.[4]
# Use as a mold
Gummed sweets such as jelly beans and wine gums are not manufactured using a mold in the conventional sense. A tray is filled with starch and leveled. A positive mold is then pressed into the starch leaving an impression of 1000 or so jelly beans. The mix is then poured into the impressions and then put into a stove to set. This method greatly reduces the number of molds that must be manufactured.
# Tests
Starch solution is used to test for iodine. A blue-black color indicates the presence of iodine in the starch solution. It is thought that the iodine fits inside the coils of amylose.[5] A 0.3% w/w solution is the standard concentration for a dilute starch indicator solution. It is made by adding 4 grams of soluble starch to 1 litre of heated water; the solution is cooled before use (starch-iodine complex becomes unstable at temperatures above 35 °C). This complex is often used in redox titrations: in presence of an oxidizing agent the solution turns blue, in the presence of reducing agent, the blue color disappears because triiodide (I3−) ions break up into three iodide ions, disassembling the complex.
Under the microscope, starch grains show a distinctive Maltese cross effect (also known as 'extinction cross' and birefringence) under polarized light.
# Starch derivatives
Starch can be hydrolyzed into simpler carbohydrates by acids, various enzymes, or a combination of the two. The extent of conversion is typically quantified by dextrose equivalent (DE), which is roughly the fraction of the glycoside bonds in starch that have been broken. Food products made in this way include:
- Maltodextrin, a lightly hydrolyzed (DE 10–20) starch product used as a bland-tasting filler and thickener.
- Various corn syrups (DE 30–70), viscous solutions used as sweeteners and thickeners in many kinds of processed foods.
- Dextrose (DE 100), commercial glucose, prepared by the complete hydrolysis of starch.
- High fructose syrup, made by treating dextrose solutions to the enzyme glucose isomerase, until a substantial fraction of the glucose has been converted to fructose. In the United States, high fructose corn syrup is the principal sweetener used in sweetened beverages because fructose tastes sweeter than glucose, and less sweetener may be used. | https://www.wikidoc.org/index.php/Starch | |
6d24165b50a8b82348ff699e6305eb5cd1efd601 | wikidoc | Sterol | Sterol
Sterols, or steroid alcohols are a subgroup of steroids with a hydroxyl group in the 3-position of the A-ring. They are amphipathic lipids synthetised from acetyl-coenzyme A. The overall molecule is quite flat. The hydroxyl group on the A ring is polar. The rest of the aliphatic chain is non-polar.
Sterols of plants are called phytosterols and sterols of animals are called zoosterols. The most important zoosterols are cholesterol and some steroid hormones; the most important phytosterols are campesterol, sitosterol, and stigmasterol.
Sterols play essential roles in the physiology of eukaryotic organisms. For example cholesterol forms part of the cellular membrane where its presence affects the cell membrane's fluidity and serves as secondary messenger in developmental signaling.
Plant sterols are also known to block cholesterol absorption sites in the human intestine thus helping to reduce cholesterol in humans.
In humans sterols act to provide important signals and metabolic communications eg. circadian rhythms, blood clotting. | Sterol
Sterols, or steroid alcohols are a subgroup of steroids with a hydroxyl group in the 3-position of the A-ring.[1] They are amphipathic lipids synthetised from acetyl-coenzyme A. The overall molecule is quite flat. The hydroxyl group on the A ring is polar. The rest of the aliphatic chain is non-polar.
Sterols of plants are called phytosterols and sterols of animals are called zoosterols. The most important zoosterols are cholesterol and some steroid hormones; the most important phytosterols are campesterol, sitosterol, and stigmasterol.
Sterols play essential roles in the physiology of eukaryotic organisms. For example cholesterol forms part of the cellular membrane where its presence affects the cell membrane's fluidity and serves as secondary messenger in developmental signaling.
Plant sterols are also known to block cholesterol absorption sites in the human intestine thus helping to reduce cholesterol in humans.
In humans sterols act to provide important signals and metabolic communications eg. circadian rhythms, blood clotting. | https://www.wikidoc.org/index.php/Sterol | |
ab8167a9ac8169318ab2a11721565505b73a2f55 | wikidoc | Stitch | Stitch
Stitch may refer to:
A method of securing thread into textiles in embroidery and sewing or creating fabrics in knitting and crochet. It may also be a method of medical care to close wounds known as sutures or stitches.
- Blanket stitch, used to reinforce the edge of thick materials
- Cable knitting is a style of knitting in which the order of stitches is permuted
- Chain stitch in which a series of looped stitches form a chain-like pattern
- Cross-stitch
- Embroidery stitch
- Garter stitch, the most basic form of welting
- Lock stitch
Other meanings:
- Side stitch, an intense stabbing pain during exercise.
- Image stitching, the process of combining multiple images to produce a panorama or high-resolution image, most commonly through the use of computer software
- "Stitch and glue", a DIY method.
- Stitch (Lilo & Stitch), one of the main characters from the 2002 41st animated Disney film Lilo & Stitch.
Stitch! The Movie, a direct-to-video animated spinoff of Lilo & Stitch, released on August 26, 2003.
Stitch!, a scheduled anime produced by Disney and Madhouse.
- Stitch! The Movie, a direct-to-video animated spinoff of Lilo & Stitch, released on August 26, 2003.
- Stitch!, a scheduled anime produced by Disney and Madhouse.
- Stitch, a fictional Canadian superheroine from Marvel Comics.
- Stitches: The Journal of Medical Humour, a Canadian humour magazine
- Stitches (Australian band), an Australian experimental music group
- The Stitches, a U.S. punk rock band
- Stitches (Welsh band), a Welsh electronica band
- Stitch (breakcore), a UK free party / breakcore artist.
- "Stitches/Dissention" is a single by American synth rock band Orgy.
- "Stitches" is a single by American hard rock band Allele.
- Rick Thomas, the sampler for Mushroomhead who goes by the alias "ST1TCH".
- Stitch, a ridge between two furrows.
- "Stitch" (slang) can also refer to a marijuana shotgun where too much tobacco makes it difficult or impossible to smoke
de:Stich | Stitch
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Stitch may refer to:
A method of securing thread into textiles in embroidery and sewing or creating fabrics in knitting and crochet. It may also be a method of medical care to close wounds known as sutures or stitches.
- Blanket stitch, used to reinforce the edge of thick materials
- Cable knitting is a style of knitting in which the order of stitches is permuted
- Chain stitch in which a series of looped stitches form a chain-like pattern
- Cross-stitch
- Embroidery stitch
- Garter stitch, the most basic form of welting
- Lock stitch
Other meanings:
- Side stitch, an intense stabbing pain during exercise.
- Image stitching, the process of combining multiple images to produce a panorama or high-resolution image, most commonly through the use of computer software
- "Stitch and glue", a DIY method.
- Stitch (Lilo & Stitch), one of the main characters from the 2002 41st animated Disney film Lilo & Stitch.
Stitch! The Movie, a direct-to-video animated spinoff of Lilo & Stitch, released on August 26, 2003.
Stitch!, a scheduled anime produced by Disney and Madhouse.
- Stitch! The Movie, a direct-to-video animated spinoff of Lilo & Stitch, released on August 26, 2003.
- Stitch!, a scheduled anime produced by Disney and Madhouse.
- Stitch, a fictional Canadian superheroine from Marvel Comics.
- Stitches: The Journal of Medical Humour, a Canadian humour magazine
- Stitches (Australian band), an Australian experimental music group
- The Stitches, a U.S. punk rock band
- Stitches (Welsh band), a Welsh electronica band
- Stitch (breakcore), a UK free party / breakcore artist.
- "Stitches/Dissention" is a single by American synth rock band Orgy.
- "Stitches" is a single by American hard rock band Allele.
- Rick Thomas, the sampler for Mushroomhead who goes by the alias "ST1TCH".
- Stitch, a ridge between two furrows.
- "Stitch" (slang) can also refer to a marijuana shotgun where too much tobacco makes it difficult or impossible to smoke
Template:Disambig
de:Stich
Template:Jb1
Template:WH
Template:WS | https://www.wikidoc.org/index.php/Stitch | |
84867e7ad693c7c5d2399a8df10bce7f45fccfbb | wikidoc | Stupor | Stupor
# Overview
Stupor is the lack of critical cognitive function and level of consciousness wherein a sufferer is almost entirely unresponsive and only responds to base stimuli such as pain. Akinesis and mutism are present but with relative preservation of conscious awareness. A person is also rigid and mute and only appears to be conscious as the eyes are open and follow surrounding objects (Gelder, Mayou and Geddes 2005).
# Historical Perspective
The word derives from the Latin stupure, meaning insensible.
# Causes
## Causes by Organ System
## Causes in Alphabetical Order
- 2-aminopyridine
- 3-aminopyridine
- Acid-base imbalance
- Acute disseminated encephalomyelitis
- Addisonian crisis
- Adrenal leukodystrophy
- Aftershave
- Alcohol abuse
- Alicyclic hydrocarbons
- Alzheimer's disease
- Aminoacidemia
- Amphetamines
- Aneurysm
- Anticholinergics
- Anticonvulsants
- Antidepressants
- Antifreeze
- Antipsychotics
- Anxiolytics
- Apraxia
- Arrhythmia
- Ativan overdose
- Bacterial meningitis
- Barbiturates
- Bartonellosis
- Basilar occlusion
- Bell mania
- Benign astrocytoma
- Bilateral anterior cerebral artery occlusion
- Bilateral internal carotid occlusion
- Bottlebrush buckeye poisoning
- Brain abscess
- Brain tumor
- Brainstem hemorrhage
- Brainstem infarction
- Brainstem thrombencephalitis
- Bristowe's syndrome
- Bromides
- Bromoform
- California buckeye poisoning
- Carbon monoxide
- Cardiac arrest
- Cardiogenic shock
- Carnitine deficiency
- Catatonia
- Catatonic depression
- Catatonic schizophrenia
- Central pontine myelinolysis
- Cerebral abscess
- Cerebral malaria
- Cerebral vasculitis
- Cologne
- Coma
- Common poppy poisoning
- Concussion
- Congestive heart failure
- Conversion disorder
- Copd
- Creutzfeldt-jakob disease
- Cyanide
- Cycad nut poisoning
- Darvocet overdose
- Dementia
- Deoderant
- Depilatories
- Depression
- Diabetic ketoacidosis
- Dialysis encephalopathy
- Dilaudid overdose
- Disseminated intravascular coagulation
- Disulfiram toxicity
- Dysarthria
- Ethylene glycol
- Exhaustion
- Fainting
- Fat embolism
- Fatal familial insomnia
- Gjessing's syndrome
- Hair bleach
- Hair dye
- Hallervorden-spatz disease
- Heart failure
- Heat stroke
- Heavy metals
- Hepatic encephalopathy
- Hereditary carnitine deficiency syndrome
- Herpes simplex encephalitis
- Hydrocarbons
- Hydrocephalus
- Hypercalcemia
- Hypercapnia
- Hypercarbia
- Hyperglycemia
- Hyperglycerolemia
- Hypergylcemic nonketotic coma
- Hypermagnesemia
- Hypernatremia
- Hyperparathyroidism
- Hypertensive crisis
- Hypertensive encephalopathy
- Hyperthermia
- Hyperthyroidism
- Hypocalcemia
- Hypoglycemia
- Hyponatremia
- Hypotension
- Hypothermia
- Hypothyroidism
- Hypoxia
- Incense
- Infectious disease
- Intracerebral bleed
- Japanese encephalitis
- Kidney failure
- Lactic acidosis
- Lead
- Lesions of the ascending reticular activation system
- Leukoencephalopathy
- Listlessness
- Lithium
- Liver encephalopathy
- Liver failure
- Lsd
- Malaise
- Malaria
- Malignant buotonneuse fever
- Marchiafava-bignami disease
- Massive or bilateral supratentorial infarction
- Mayapple poisoning
- Meningitis
- Mental illness
- Methanol
- Midline brainstem tumor
- Milkweed poisoning
- Monoamine oxidase inhibitors
- Morphine overdose
- Multifocal leukoencephalopathy
- Multiple sclerosis
- Mushrooms
- Myocardial infarction
- Nabilone
- Narcotics
- Near drowning
- Neuroleptic malignant syndrome
- Nonbacterial thrombotic endocarditis
- Nonconvulsive status epilepticus
- Oil-based paint
- Ophthalmoparesis
- Opiates
- Other hypnotics
- Paraldehyde
- Pergolide
- Phencylidine
- Pituitary apoplexy
- Pontine hemorrhage
- Porphyria
- Postictal seizure
- Postinfectious encephalomyelitis
- Propylene glycol
- Prostration
- Psychotropics
- Puerperal psychosis
- Red buckeye poisoning
- Renal insufficiency
- Respiratory acidosis
- Reye's encephalopathy
- Rickettsial disease
- Sagittal sinus thrombosis
- Salicylate
- Schizophrenia
- Sedatives
- Seizure
- Sensory ataxic neuropathy
- Sepsis
- Serratia cerebral abscess
- Serratia meningitis
- Severe depression
- Sodium monofluoroacetate
- Stroke
- Subacute bacterial endocarditis
- Subacute sclerosing leukoencephalitis
- Subarachnoid hemorrhage
- Subdural empyema
- Subdural hemorrhage bilateral
- Syncope
- Syphilis
- Thalamic hemorrhage
- Thallium
- Thrombophlebitis
- Thrombotic thrombocytopenic purpura
- Tranquilizers
- Trauma-contusion
- Tumor
- Typhoid fever
- Typhus
- Unilateral hemispheric mass
- Uremia
- Variant cjd
- Vascular diseases
- Viral encephalitis
- Vitamin d deficiency
- Waterhouse-friderichsen syndrome
- Wernicke's encephalopathy
# Differentiating Stupor from other Diseases
Stupor is not the same thing as a coma or a vegetative state. For example, some people who become injured suddenly with a concussion or some other cognitive impairment resulting from injury enter a stupor, where they are partially aware of their surroundings, or they become unconscious until they are revived by themselves or by others. Stupor may be mistaken for delirium and may be treated with Haldol and / or other anti-psychotic drugs.
# Diagnosis
## History and Symptoms
If not stimulated externally, a patient with stupor will be in a sleepy mode most of the time. In some extreme cases of severe depressive disorders the patient can become motionless, lose their appetite and become mute. Short periods of restricted responsivity can be achieved by intense stimulation (e.g. pain, bright light, loud noise).
Questions about the patients medical history and symptoms should include:
- Time pattern
When did the decreased alertness happen?
How long did it last?
Has it ever happened before? If so, how many times?
Did the person behave the same way during past episodes?
- When did the decreased alertness happen?
- How long did it last?
- Has it ever happened before? If so, how many times?
- Did the person behave the same way during past episodes?
- Medical history
Does the person have epilepsy or a seizure disorder?
Does the person have diabetes?
Has the person been sleeping well?
Has there been a recent head injury?
- Does the person have epilepsy or a seizure disorder?
- Does the person have diabetes?
- Has the person been sleeping well?
- Has there been a recent head injury?
- Other
What medications does the person take?
Does the person use alcohol or drugs on a regular basis?
What other symptoms are present?
- What medications does the person take?
- Does the person use alcohol or drugs on a regular basis?
- What other symptoms are present?
## CT
Lesions of the Ascending Reticular Activation System on height of the pons and metencephalon have been shown to cause stupor. The incidence is higher after left-sided lesions.
# Treatment
Treatment depends on the cause of the decreased alertness. How well a person does depends on the cause of the condition.
# Related Chapters
- Torpor | Stupor
For patient information, click here
Template:Search infobox
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Stupor is the lack of critical cognitive function and level of consciousness wherein a sufferer is almost entirely unresponsive and only responds to base stimuli such as pain. Akinesis and mutism are present but with relative preservation of conscious awareness. A person is also rigid and mute and only appears to be conscious as the eyes are open and follow surrounding objects (Gelder, Mayou and Geddes 2005).
# Historical Perspective
The word derives from the Latin stupure, meaning insensible.
# Causes
## Causes by Organ System
## Causes in Alphabetical Order
- 2-aminopyridine
- 3-aminopyridine
- Acid-base imbalance
- Acute disseminated encephalomyelitis
- Addisonian crisis
- Adrenal leukodystrophy
- Aftershave
- Alcohol abuse
- Alicyclic hydrocarbons
- Alzheimer's disease
- Aminoacidemia
- Amphetamines
- Aneurysm
- Anticholinergics
- Anticonvulsants
- Antidepressants
- Antifreeze
- Antipsychotics
- Anxiolytics
- Apraxia
- Arrhythmia
- Ativan overdose
- Bacterial meningitis
- Barbiturates
- Bartonellosis
- Basilar occlusion
- Bell mania
- Benign astrocytoma
- Bilateral anterior cerebral artery occlusion
- Bilateral internal carotid occlusion
- Bottlebrush buckeye poisoning
- Brain abscess
- Brain tumor
- Brainstem hemorrhage
- Brainstem infarction
- Brainstem thrombencephalitis
- Bristowe's syndrome
- Bromides
- Bromoform
- California buckeye poisoning
- Carbon monoxide
- Cardiac arrest
- Cardiogenic shock
- Carnitine deficiency
- Catatonia
- Catatonic depression
- Catatonic schizophrenia
- Central pontine myelinolysis
- Cerebral abscess
- Cerebral malaria
- Cerebral vasculitis
- Cologne
- Coma
- Common poppy poisoning
- Concussion
- Congestive heart failure
- Conversion disorder
- Copd
- Creutzfeldt-jakob disease
- Cyanide
- Cycad nut poisoning
- Darvocet overdose
- Dementia
- Deoderant
- Depilatories
- Depression
- Diabetic ketoacidosis
- Dialysis encephalopathy
- Dilaudid overdose
- Disseminated intravascular coagulation
- Disulfiram toxicity
- Dysarthria
- Ethylene glycol
- Exhaustion
- Fainting
- Fat embolism
- Fatal familial insomnia
- Gjessing's syndrome
- Hair bleach
- Hair dye
- Hallervorden-spatz disease
- Heart failure
- Heat stroke
- Heavy metals
- Hepatic encephalopathy
- Hereditary carnitine deficiency syndrome
- Herpes simplex encephalitis
- Hydrocarbons
- Hydrocephalus
- Hypercalcemia
- Hypercapnia
- Hypercarbia
- Hyperglycemia
- Hyperglycerolemia
- Hypergylcemic nonketotic coma
- Hypermagnesemia
- Hypernatremia
- Hyperparathyroidism
- Hypertensive crisis
- Hypertensive encephalopathy
- Hyperthermia
- Hyperthyroidism
- Hypocalcemia
- Hypoglycemia
- Hyponatremia
- Hypotension
- Hypothermia
- Hypothyroidism
- Hypoxia
- Incense
- Infectious disease
- Intracerebral bleed
- Japanese encephalitis
- Kidney failure
- Lactic acidosis
- Lead
- Lesions of the ascending reticular activation system
- Leukoencephalopathy
- Listlessness
- Lithium
- Liver encephalopathy
- Liver failure
- Lsd
- Malaise
- Malaria
- Malignant buotonneuse fever
- Marchiafava-bignami disease
- Massive or bilateral supratentorial infarction
- Mayapple poisoning
- Meningitis
- Mental illness
- Methanol
- Midline brainstem tumor
- Milkweed poisoning
- Monoamine oxidase inhibitors
- Morphine overdose
- Multifocal leukoencephalopathy
- Multiple sclerosis
- Mushrooms
- Myocardial infarction
- Nabilone
- Narcotics
- Near drowning
- Neuroleptic malignant syndrome
- Nonbacterial thrombotic endocarditis
- Nonconvulsive status epilepticus
- Oil-based paint
- Ophthalmoparesis
- Opiates
- Other hypnotics
- Paraldehyde
- Pergolide
- Phencylidine
- Pituitary apoplexy
- Pontine hemorrhage
- Porphyria
- Postictal seizure
- Postinfectious encephalomyelitis
- Propylene glycol
- Prostration
- Psychotropics
- Puerperal psychosis
- Red buckeye poisoning
- Renal insufficiency
- Respiratory acidosis
- Reye's encephalopathy
- Rickettsial disease
- Sagittal sinus thrombosis
- Salicylate
- Schizophrenia
- Sedatives
- Seizure
- Sensory ataxic neuropathy
- Sepsis
- Serratia cerebral abscess
- Serratia meningitis
- Severe depression
- Sodium monofluoroacetate
- Stroke
- Subacute bacterial endocarditis
- Subacute sclerosing leukoencephalitis
- Subarachnoid hemorrhage
- Subdural empyema
- Subdural hemorrhage bilateral
- Syncope
- Syphilis
- Thalamic hemorrhage
- Thallium
- Thrombophlebitis
- Thrombotic thrombocytopenic purpura
- Tranquilizers
- Trauma-contusion
- Tumor
- Typhoid fever
- Typhus
- Unilateral hemispheric mass
- Uremia
- Variant cjd
- Vascular diseases
- Viral encephalitis
- Vitamin d deficiency
- Waterhouse-friderichsen syndrome
- Wernicke's encephalopathy
# Differentiating Stupor from other Diseases
Stupor is not the same thing as a coma or a vegetative state. For example, some people who become injured suddenly with a concussion or some other cognitive impairment resulting from injury enter a stupor, where they are partially aware of their surroundings, or they become unconscious until they are revived by themselves or by others. Stupor may be mistaken for delirium and may be treated with Haldol and / or other anti-psychotic drugs.
# Diagnosis
## History and Symptoms
If not stimulated externally, a patient with stupor will be in a sleepy mode most of the time. In some extreme cases of severe depressive disorders the patient can become motionless, lose their appetite and become mute. Short periods of restricted responsivity can be achieved by intense stimulation (e.g. pain, bright light, loud noise).
Questions about the patients medical history and symptoms should include:
- Time pattern
When did the decreased alertness happen?
How long did it last?
Has it ever happened before? If so, how many times?
Did the person behave the same way during past episodes?
- When did the decreased alertness happen?
- How long did it last?
- Has it ever happened before? If so, how many times?
- Did the person behave the same way during past episodes?
- Medical history
Does the person have epilepsy or a seizure disorder?
Does the person have diabetes?
Has the person been sleeping well?
Has there been a recent head injury?
- Does the person have epilepsy or a seizure disorder?
- Does the person have diabetes?
- Has the person been sleeping well?
- Has there been a recent head injury?
- Other
What medications does the person take?
Does the person use alcohol or drugs on a regular basis?
What other symptoms are present?
- What medications does the person take?
- Does the person use alcohol or drugs on a regular basis?
- What other symptoms are present?
## CT
Lesions of the Ascending Reticular Activation System on height of the pons and metencephalon have been shown to cause stupor. The incidence is higher after left-sided lesions.
# Treatment
Treatment depends on the cause of the decreased alertness. How well a person does depends on the cause of the condition.
# Related Chapters
- Torpor | https://www.wikidoc.org/index.php/Stupor | |
981ebf78dc19573bcbef22b7aa39fe01f7d142d8 | wikidoc | Supima | Supima
Supima is a non-profit organisation in the United States whose main objective is to promote the use of American Pima cotton around the world and is involved in quality assurance and research programs. Founded in 1954, it derived its name from superior pima.
Supima licenses over 300 selected high-quality mills, textile and clothing manufacturers, and retailers to use the Supima® trademark. Members finance the activities of Supima by payments calculated on a "per bale" basis.
Its other activities include:
- research programs to improve the quality of American Pima cotton
- timely crop and market information to its grower-members and licensees
- advertisements in both consumer and trade publications
- presentations to customers both in the USA and abroad
- participation in major international exhibitions and events
The Board of Directors of Supima is made up of Pima growers from Arizona, California, New Mexico and Texas.
Production of Supima cotton has risen from about 100,000 bales per year in the 1980s to over 800,000 bales in 2006. More than 90% of Supima cotton is exported from the United States, the majority of this being for the overseas manufacture of finished fabrics, clothing, sheets and towels which are re-exported to the United States for sale. The top five importers of Supima cotton are China, Pakistan, India, Japan and Indonesia. | Supima
Supima is a non-profit organisation in the United States whose main objective is to promote the use of American Pima cotton around the world[1] and is involved in quality assurance and research programs. Founded in 1954, it derived its name from superior pima.[2]
Supima licenses over 300 selected high-quality mills, textile and clothing manufacturers, and retailers to use the Supima® trademark. Members finance the activities of Supima by payments calculated on a "per bale" basis.
Its other activities include:[1]
- research programs to improve the quality of American Pima cotton
- timely crop and market information to its grower-members and licensees
- advertisements in both consumer and trade publications
- presentations to customers both in the USA and abroad
- participation in major international exhibitions and events
The Board of Directors of Supima is made up of Pima growers from Arizona, California, New Mexico and Texas.[3]
Production of Supima cotton has risen from about 100,000 bales per year in the 1980s to over 800,000 bales in 2006. More than 90% of Supima cotton is exported from the United States, the majority of this being for the overseas manufacture of finished fabrics, clothing, sheets and towels which are re-exported to the United States for sale. The top five importers of Supima cotton are China, Pakistan, India, Japan and Indonesia.[2] | https://www.wikidoc.org/index.php/Supima | |
9c1a5f8cce12b10ff32826689f12dfc6c9cdc900 | wikidoc | Suture | Suture
A suture is a medical device that doctors, and especially surgeons, use to hold skin, internal organs, blood vessels and all other tissues of the human body together, after they have been severed by injury or surgery. They must be strong (so they do not break), non-toxic and hypoallergenic (to avoid adverse reactions in the body), and flexible (so they can be tied and knotted easily). In addition, they must lack the so called "wick effect", which means that sutures must not allow fluids to penetrate the body through them from outside, which could easily cause infections.
# Absorbable and nonabsorbable sutures
Sutures are divided into two kinds - those which are absorbable and will break down harmlessly in the body over time without intervention, and those which are non-absorbable and must be manually removed if they are not left indefinitely. The type of suture used varies on the operation, with the major criteria being the demands of the location and environment.
- Sutures to be placed internally would require re-opening if they were to be removed. Sutures which lie on the exterior of the body can be removed within minutes, and without re-opening the wound. As a result, absorbable sutures are often used internally; non-absorbable externally.
- Sutures to be placed in a stressful environment, for example the heart (constant pressure and movement) or the bladder (adverse chemical presence) may require specialized or stronger materials to perform their role; usually such sutures are either specially treated, or made of special materials, and are often non-absorbable to reduce the risk of degradation.
## Absorbable sutures
Absorbable sutures are made of materials which are broken down in tissue after a given period of time, which depending on the material can be from ten days to eight weeks. They are used therefore in many of the internal tissues of the body. In most cases, three weeks is sufficient for the wound to close firmly. The suture is not needed any more, and the fact that it disappears is an advantage, as there is no foreign material left inside the body and no need for the patient to have the sutures removed.
Absorbable sutures were originally made of the intestines of sheep, the so called catgut. The manufacturing process was similar to that of natural musical strings for violins and guitar, and also of natural strings for tennis racquets. The inventor, a 10th century surgeon named al-Zahrawi reportedly discovered the dissolving nature of catgut when his lute's strings were eaten by a monkey. Today, gut sutures are made of specially prepared beef and sheep intestine, and may be untreated (plain gut), tanned with chromium salts to increase their persistence in the body (chromic gut), or heat-treated to give more rapid absorption (fast gut). However, the major part of the absorbable sutures used are now made of synthetic polymer fibers, which may be braided or monofilament; these offer numerous advantages over gut sutures, notably ease of handling, low cost, low tissue reaction, consistent performance and guaranteed non-toxicity. In Europe and Japan, gut sutures have been banned due to concerns over bovine spongiform encephalopathy (mad-cow disease), although the herds from which gut is harvested are certified BSE-free. Each major suture manufacturer has its own proprietary formulations for its brands of synthetic absorbable sutures; various blends of polyglycolic acid (Biovek for example), lactic acid or caprolactone are common.
Occasionally, absorbable sutures can cause inflammation and be rejected by the body rather than absorbed.
## Non-absorbable sutures
Nonabsorbable sutures are made of materials which are not metabolized by the body, and are used therefore either on skin wound closure, where the sutures can be removed after a few weeks, or in some inner tissues in which absorbable sutures are not adequate. This is the case, for example, in the heart and in blood vessels, whose rhythmic movement requires a suture which stays longer than three weeks, to give the wound enough time to close. Other organs, like the bladder, contain fluids which make absorbable sutures disappear in only a few days, too early for the wound to heal. Inflammation caused by the foreign protein in some absorbable sutures can amplify scarring, so if other types of suture are less antigenic (ie, do not provoke as much of an immune response) it would represent a way to reduce scarring.
There are several materials used for nonabsorbable sutures. The most common is a natural fiber, silk, which undergoes a special manufacturing process to make it adequate for its use in surgery. Other nonabsorbable sutures are made of artificial fibers, like polypropylene, polyester or nylon; these may or may not have coatings to enhance their performance characteristics. Finally, stainless steel wires are commonly used in orthopedic surgery and for sternal closure in cardiac surgery.
# Surgical needles for use with sutures
Traumatic needles are needles with holes or eyes which are supplied to the hospital separate from their suture thread. The suture must be threaded on site, as is done when sewing at home. Atraumatic needles with sutures comprise an eyeless needle attached to a specific length of suture thread. The suture manufacturer swages the suture thread to the eyeless atraumatic needle at the factory. There are several advantages to having the needle pre-mounted on the suture. The doctor or the nurse or odp does not have to spend time threading the suture on the needle. More important, the suture end of a swaged needle is smaller than the needle body. In traumatic needles with eyes, the thread comes out of the needle's hole on both sides. When passing through the tissues, this type of suture rips the tissue to a certain extent, thus the name traumatic. Nearly all modern sutures feature swaged atraumatic needles.
There are several shapes of surgical needles, including:
- straight
- half curved or ski
- 1/4 circle
- 3/8 circle
- 1/2 circle
- 5/8 circle
- compound curve
Needles may also be classified by their point geometry; examples include:
- taper (needle body is round and tapers smoothly to a point)
- cutting (needle body is triangular and has a sharpened cutting edge on the inside)
- reverse cutting (cutting edge on the outside)
- trocar point or tapercut (needle body is round and tapered, but ends in a small triangular cutting point)
- blunt points for sewing friable tissues
- side cutting or spatula points (flat on top and bottom with a cutting edge along the front to one side) for eye surgery
Finally, atraumatic needles may be permanently swaged to the suture or may be designed to come off the suture with a sharp straight tug. These "pop-offs" are commonly used for interrupted sutures, where each suture is only passed once and then tied.
# Sizes of sutures
Suture sizes are defined by the United States Pharmacopeia (U.S.P.). Sutures were originally manufactured ranging in size from #1 to #6, with #1 being the smallest. A #4 suture would be roughly the diameter of a tennis racquet string. The manufacturing techniques, derived at the beginning from the production of musical strings, did not allow thinner diameters. As the procedures improved, #0 was added to the suture diameters, and later, thinner and thinner threads were manufactured, which were identified as #00 (#2-0 or #2/0) to #000000 (#6-0 or #6/0).
Modern sutures range from #5 (heavy braided suture for orthopedics) to #11-0 (fine monofilament suture for ophthalmics). Atraumatic needles are manufactured in all shapes for most sizes. The actual diameter of thread for a given U.S.P. size differs depending on the suture material class.
# Suture techniques
Common suture stitching techniques include:
- Simple Interrupted Stitch
- Running Stitch
- Mattress
- Horizontal mattress
- Vertical mattress
- Figure 8
- Continuous locking
- Subcuticular
# Removal of sutures
Whilst some sutures are intended to be permanent, and others in specialized cases may be kept in place for an extended period of many weeks, as a rule sutures are a short term device to allow healing of a trauma or wound. According to about.com's article on nursing:
# Suture materials
# U.S.P. Needle Pull Specifications
# Other facts
## Tissue adhesives
In recent years, topical cyanoacrylate adhesives ("liquid stitches") have been used in combination with, or as an alternative to, sutures in wound closure. The adhesive remains liquid until exposed to water or water-containing substances/tissue, after which it cures (polymerizes) and forms a flexible film that bonds to the underlying surface. The tissue adhesive has been shown to act as a barrier to microbial penetration as long as the adhesive film remains intact. Limitations of tissue adhesives include contraindications to use near the eyes and a mild learning curve on correct usage.
## Antimicrobial sutures
Another recent development in wound closure involves the use of sutures coated with antimicrobial substances to reduce the chances of wound infection. While long-term studies are not yet available, preliminary results indicate that these sutures are effective at keeping bacteria out of wounds. | Suture
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
A suture is a medical device that doctors, and especially surgeons, use to hold skin, internal organs, blood vessels and all other tissues of the human body together, after they have been severed by injury or surgery. They must be strong (so they do not break), non-toxic and hypoallergenic (to avoid adverse reactions in the body), and flexible (so they can be tied and knotted easily). In addition, they must lack the so called "wick effect", which means that sutures must not allow fluids to penetrate the body through them from outside, which could easily cause infections.
# Absorbable and nonabsorbable sutures
Sutures are divided into two kinds - those which are absorbable and will break down harmlessly in the body over time without intervention, and those which are non-absorbable and must be manually removed if they are not left indefinitely. The type of suture used varies on the operation, with the major criteria being the demands of the location and environment.
- Sutures to be placed internally would require re-opening if they were to be removed. Sutures which lie on the exterior of the body can be removed within minutes, and without re-opening the wound. As a result, absorbable sutures are often used internally; non-absorbable externally.
- Sutures to be placed in a stressful environment, for example the heart (constant pressure and movement) or the bladder (adverse chemical presence) may require specialized or stronger materials to perform their role; usually such sutures are either specially treated, or made of special materials, and are often non-absorbable to reduce the risk of degradation.
## Absorbable sutures
Absorbable sutures are made of materials which are broken down in tissue after a given period of time, which depending on the material can be from ten days to eight weeks. They are used therefore in many of the internal tissues of the body. In most cases, three weeks is sufficient for the wound to close firmly. The suture is not needed any more, and the fact that it disappears is an advantage, as there is no foreign material left inside the body and no need for the patient to have the sutures removed.
Absorbable sutures were originally made of the intestines of sheep, the so called catgut. The manufacturing process was similar to that of natural musical strings for violins and guitar, and also of natural strings for tennis racquets. The inventor, a 10th century surgeon named al-Zahrawi reportedly discovered the dissolving nature of catgut when his lute's strings were eaten by a monkey. Today, gut sutures are made of specially prepared beef and sheep intestine, and may be untreated (plain gut), tanned with chromium salts to increase their persistence in the body (chromic gut), or heat-treated to give more rapid absorption (fast gut). However, the major part of the absorbable sutures used are now made of synthetic polymer fibers, which may be braided or monofilament; these offer numerous advantages over gut sutures, notably ease of handling, low cost, low tissue reaction, consistent performance and guaranteed non-toxicity. In Europe and Japan, gut sutures have been banned due to concerns over bovine spongiform encephalopathy (mad-cow disease), although the herds from which gut is harvested are certified BSE-free. Each major suture manufacturer has its own proprietary formulations for its brands of synthetic absorbable sutures; various blends of polyglycolic acid (Biovek for example), lactic acid or caprolactone are common.
Occasionally, absorbable sutures can cause inflammation and be rejected by the body rather than absorbed.
## Non-absorbable sutures
Nonabsorbable sutures are made of materials which are not metabolized by the body, and are used therefore either on skin wound closure, where the sutures can be removed after a few weeks, or in some inner tissues in which absorbable sutures are not adequate. This is the case, for example, in the heart and in blood vessels, whose rhythmic movement requires a suture which stays longer than three weeks, to give the wound enough time to close. Other organs, like the bladder, contain fluids which make absorbable sutures disappear in only a few days, too early for the wound to heal. Inflammation caused by the foreign protein in some absorbable sutures can amplify scarring, so if other types of suture are less antigenic (ie, do not provoke as much of an immune response) it would represent a way to reduce scarring.
There are several materials used for nonabsorbable sutures. The most common is a natural fiber, silk, which undergoes a special manufacturing process to make it adequate for its use in surgery. Other nonabsorbable sutures are made of artificial fibers, like polypropylene, polyester or nylon; these may or may not have coatings to enhance their performance characteristics. Finally, stainless steel wires are commonly used in orthopedic surgery and for sternal closure in cardiac surgery.
# Surgical needles for use with sutures
Traumatic needles are needles with holes or eyes which are supplied to the hospital separate from their suture thread. The suture must be threaded on site, as is done when sewing at home. Atraumatic needles with sutures comprise an eyeless needle attached to a specific length of suture thread. The suture manufacturer swages the suture thread to the eyeless atraumatic needle at the factory. There are several advantages to having the needle pre-mounted on the suture. The doctor or the nurse or odp does not have to spend time threading the suture on the needle. More important, the suture end of a swaged needle is smaller than the needle body. In traumatic needles with eyes, the thread comes out of the needle's hole on both sides. When passing through the tissues, this type of suture rips the tissue to a certain extent, thus the name traumatic. Nearly all modern sutures feature swaged atraumatic needles.
There are several shapes of surgical needles, including:
- straight
- half curved or ski
- 1/4 circle
- 3/8 circle
- 1/2 circle
- 5/8 circle
- compound curve
Needles may also be classified by their point geometry; examples include:
- taper (needle body is round and tapers smoothly to a point)
- cutting (needle body is triangular and has a sharpened cutting edge on the inside)
- reverse cutting (cutting edge on the outside)
- trocar point or tapercut (needle body is round and tapered, but ends in a small triangular cutting point)
- blunt points for sewing friable tissues
- side cutting or spatula points (flat on top and bottom with a cutting edge along the front to one side) for eye surgery
Finally, atraumatic needles may be permanently swaged to the suture or may be designed to come off the suture with a sharp straight tug. These "pop-offs" are commonly used for interrupted sutures, where each suture is only passed once and then tied.
# Sizes of sutures
Suture sizes are defined by the United States Pharmacopeia (U.S.P.). Sutures were originally manufactured ranging in size from #1 to #6, with #1 being the smallest. A #4 suture would be roughly the diameter of a tennis racquet string. The manufacturing techniques, derived at the beginning from the production of musical strings, did not allow thinner diameters. As the procedures improved, #0 was added to the suture diameters, and later, thinner and thinner threads were manufactured, which were identified as #00 (#2-0 or #2/0) to #000000 (#6-0 or #6/0).
Modern sutures range from #5 (heavy braided suture for orthopedics) to #11-0 (fine monofilament suture for ophthalmics). Atraumatic needles are manufactured in all shapes for most sizes. The actual diameter of thread for a given U.S.P. size differs depending on the suture material class.
# Suture techniques
Common suture stitching techniques include:
- Simple Interrupted Stitch
- Running Stitch
- Mattress
- Horizontal mattress
- Vertical mattress
- Figure 8
- Continuous locking
- Subcuticular
# Removal of sutures
Whilst some sutures are intended to be permanent, and others in specialized cases may be kept in place for an extended period of many weeks, as a rule sutures are a short term device to allow healing of a trauma or wound. According to about.com's article on nursing:[1]
# Suture materials
# U.S.P. Needle Pull Specifications
# Other facts
## Tissue adhesives
In recent years, topical cyanoacrylate adhesives ("liquid stitches") have been used in combination with, or as an alternative to, sutures in wound closure. The adhesive remains liquid until exposed to water or water-containing substances/tissue, after which it cures (polymerizes) and forms a flexible film that bonds to the underlying surface. The tissue adhesive has been shown to act as a barrier to microbial penetration as long as the adhesive film remains intact. Limitations of tissue adhesives include contraindications to use near the eyes and a mild learning curve on correct usage.
## Antimicrobial sutures
Another recent development in wound closure involves the use of sutures coated with antimicrobial substances to reduce the chances of wound infection. While long-term studies are not yet available, preliminary results indicate that these sutures are effective at keeping bacteria out of wounds. | https://www.wikidoc.org/index.php/Surgical_thread | |
f54674de2d60c32f340c9e622951849cf48af4bc | wikidoc | Syngas | Syngas
# Overview
Syngas (from synthesis gas) is the name given to a gas mixture that contains varying amounts of carbon monoxide and hydrogen generated by the gasification of a carbon containing fuel to a gaseous product with a heating value. Examples include steam reforming of natural gas or liquid hydrocarbons to produce hydrogen, the gasification of coal and in some types of waste-to-energy gasification facilities. The name comes from their use as intermediates in creating synthetic natural gas (SNG) and for producing ammonia or methanol. Syngas is also used as an intermediate in producing synthetic petroleum for use as a fuel or lubricant via Fischer-Tropsch synthesis and previously the Mobil methanol to gasoline process.
Syngas consists primarily of carbon monoxide, carbon dioxide and hydrogen, and has less than half the energy density of natural gas. Syngas is combustible and often used as a fuel source or as an intermediate for the production of other chemicals. Syngas for use as a fuel is most often produced by gasification of coal or municipal waste mainly by the following paths:
When used as an intermediate in the large-scale, industrial synthesis of hydrogen and ammonia, it is also produced from natural gas (via the steam reforming reaction) as follows:
The syngas produced in large waste-to-energy gasification facilities is used as fuel to generate electricity.
Coal gasification processes are reasonably efficient and were used for many years to manufacture illuminating gas (coal gas) for gas lighting, before electric lighting became widely available.
When syngas contains a significant amount of nitrogen, the nitrogen must be removed. Cryogenic processing has great difficulty in recovering pure carbon monoxide when relatively large volumes of nitrogen are present due to carbon monoxide and nitrogen having very similar boiling points which are -191.5 °C and -195.79 °C respectively. Certain process technology selectively removes carbon monoxide by complexation/decomplexation of carbon monoxide with cuprous aluminum chloride (CuAlCl4), dissolved in an organic liquid such as toluene. The purified carbon monoxide can have a purity greater than 99%, which makes it a good feedstock for the chemical industry. The reject gas from the system can contain carbon dioxide, nitrogen, methane, ethane and hydrogen. The reject gas can be further processed on a pressure swing absorption system to remove hydrogen and the hydrogen and carbon dioxide can be recombined in the proper ratio for methanol production, Fischer-Tropsch diesel etc. However, the total energy efficiency is not very high, if the gas is used to make fuel, meaning that the purification processes are very energy intensive. | Syngas
Template:Seealso
# Overview
Syngas (from synthesis gas) is the name given to a gas mixture that contains varying amounts of carbon monoxide and hydrogen generated by the gasification of a carbon containing fuel to a gaseous product with a heating value. Examples include steam reforming of natural gas or liquid hydrocarbons to produce hydrogen, the gasification of coal[1] and in some types of waste-to-energy gasification facilities. The name comes from their use as intermediates in creating synthetic natural gas (SNG)[2] and for producing ammonia or methanol. Syngas is also used as an intermediate in producing synthetic petroleum for use as a fuel or lubricant via Fischer-Tropsch synthesis and previously the Mobil methanol to gasoline process.
Syngas consists primarily of carbon monoxide, carbon dioxide and hydrogen, and has less than half the energy density of natural gas. Syngas is combustible and often used as a fuel source or as an intermediate for the production of other chemicals. Syngas for use as a fuel is most often produced by gasification of coal or municipal waste mainly by the following paths:
When used as an intermediate in the large-scale, industrial synthesis of hydrogen and ammonia, it is also produced from natural gas (via the steam reforming reaction) as follows:
The syngas produced in large waste-to-energy gasification facilities is used as fuel to generate electricity.[3]
Coal gasification processes are reasonably efficient and were used for many years to manufacture illuminating gas (coal gas) for gas lighting, before electric lighting became widely available.
When syngas contains a significant amount of nitrogen, the nitrogen must be removed. Cryogenic processing has great difficulty in recovering pure carbon monoxide when relatively large volumes of nitrogen are present due to carbon monoxide and nitrogen having very similar boiling points which are -191.5 °C and -195.79 °C respectively. Certain process technology selectively removes carbon monoxide by complexation/decomplexation of carbon monoxide with cuprous aluminum chloride (CuAlCl4), dissolved in an organic liquid such as toluene. The purified carbon monoxide can have a purity greater than 99%, which makes it a good feedstock for the chemical industry. The reject gas from the system can contain carbon dioxide, nitrogen, methane, ethane and hydrogen. The reject gas can be further processed on a pressure swing absorption system to remove hydrogen and the hydrogen and carbon dioxide can be recombined in the proper ratio for methanol production, Fischer-Tropsch diesel etc. However, the total energy efficiency is not very high, if the gas is used to make fuel, meaning that the purification processes are very energy intensive. | https://www.wikidoc.org/index.php/Syngas | |
d36bec8223bfb52a90094b01f23492a59fa56a8a | wikidoc | Syntex | Syntex
Laboratorios Syntex SA was a pharmaceutical company formed in Mexico City in 1944 by Russell Marker to manufacture therapeutic steroids from the Mexican yam. Syntex was integrated into the Roche group in 1994.
# Prominent researchers
- Russell Marker left the company and took his notebooks in a disagreement over compensation.
- George Rosenkranz had studied at the Swiss Federal Institute of Technology and was conducting pharmaceutical research in Cuba. He joined Syntex to replace Marker and hired Djerassi.
- Carl Djerassi went to work at Syntex in 1949 as the associate director of chemical research. He oversaw the research resulting in the first synthesis of norethindrone, the first orally active progestin, which led to the development of some of the first oral contraceptives.
- Luis E. Miramontes moved from UNAM to Syntex in 1950 as a researcher under the direction of Djerassi. He performed the first synthesis of an orally active progestin on October 15, 1951. The steroid was 19-nor-17 alpha-ethynyltestosterone, with the generic name of norethistrone or norethindrone, which led to the development of some of the first oral contraceptives.
# Birth control pill
Syntex submitted their compound to a laboratory in Madison, Wisconsin, for biological evaluation, and found it was the most active, orally-effective progestational hormone of its time. Syntex submitted a patent application in November of 1951. G.D. Searle & Co. filed for a patent for the synthesis of the double bond isomer 13 of norethindrone called norethynodrel in August of 1953. Norethynodrel is converted into norethindrone under acidic conditions, and their new patent didn't infringe on Syntex's. Searle obtained approval to market norethynodrel before Syntex received their approval. By 1964, 3 companies including Syntex were marketing 2 mg doses of Syntex's norethindrone. Syntex chemists synthesized cortisone from diosgenin, a phytosteroid contained in Mexican yams. This synthesis was a more economical than the previous Merck & Co. synthesis. | Syntex
Laboratorios Syntex SA was a pharmaceutical company formed in Mexico City in 1944 by Russell Marker to manufacture therapeutic steroids from the Mexican yam. Syntex was integrated into the Roche group in 1994.
# Prominent researchers
- Russell Marker left the company and took his notebooks in a disagreement over compensation.
- George Rosenkranz had studied at the Swiss Federal Institute of Technology and was conducting pharmaceutical research in Cuba. He joined Syntex to replace Marker and hired Djerassi.
- Carl Djerassi went to work at Syntex in 1949 as the associate director of chemical research. He oversaw the research resulting in the first synthesis of norethindrone, the first orally active progestin, which led to the development of some of the first oral contraceptives.
- Luis E. Miramontes moved from UNAM to Syntex in 1950 as a researcher under the direction of Djerassi. He performed the first synthesis of an orally active progestin on October 15, 1951. The steroid was 19-nor-17 alpha-ethynyltestosterone, with the generic name of norethistrone or norethindrone, which led to the development of some of the first oral contraceptives.
# Birth control pill
Syntex submitted their compound to a laboratory in Madison, Wisconsin, for biological evaluation, and found it was the most active, orally-effective progestational hormone of its time. Syntex submitted a patent application in November of 1951. G.D. Searle & Co. filed for a patent for the synthesis of the double bond isomer 13 of norethindrone called norethynodrel in August of 1953. Norethynodrel is converted into norethindrone under acidic conditions, and their new patent didn't infringe on Syntex's. Searle obtained approval to market norethynodrel before Syntex received their approval. By 1964, 3 companies including Syntex were marketing 2 mg doses of Syntex's norethindrone. Syntex chemists synthesized cortisone from diosgenin, a phytosteroid contained in Mexican yams. This synthesis was a more economical than the previous Merck & Co. synthesis. | https://www.wikidoc.org/index.php/Syntex | |
0d81efb0fed19473e9d9eed8f4e46c8112510c06 | wikidoc | T wave | T wave
# Overview
The T wave represents the repolarization (or recovery) of the ventricles. The interval from the beginning of the QRS complex to the apex of the T wave is referred to as the absolute refractory period. The last half of the T wave is referred to as the relative refractory period (or vulnerable period).
# Orientation of T waves
## Normal Orientation
### General
- Normally upright in leads 1 and 2 and in the chest leads over the left ventricle.
### Precordial Leads
- Lead V1 may have a positive, negative, or biphasic T wave.
- The T wave in V1 may be inverted at any age (is more often inverted than upright) and the T in V2 can normally be inverted.
- When the T in V1 is upright, it is almost never as tall as the T in V6.
- In infants and young children precordial T waves may be inverted.
- In adult males it is considered abnormal if the T waves are inverted as far to the left as lead V3.
- In adult females the T in V3 may be shallowly inverted.
### aVF
- Normally upright in aVL and aVF if the QRS is > 5 mm tall but may be inverted if the R waves are smaller.
- It is not uncommon to have an isolated negative T wave in lead III, aVL, or aVF. Cardiologists are often asked to consult pre-operativley on the patient with the isolated flipped T in lead III.
### aVR
- Normally inverted in aVR.
### In The Presence of Conduction Delay
- When a conduction abnormality (e.g., left bundle branch block,right bundle branch block, or a paced rhythm) is present, the T wave should be deflected opposite the terminal deflection of the QRS complex. This is known as appropriate T wave discordance. If the T waves are oriented in the same direction as the QRS complex, this is termed T wave concordance, and may be a sign of ischemia in the presence of left bundle branch block.
### Differential Diagnosis of Inverted or Negative T waves:
- Coronary ischemia
- Left ventricular hypertrophy
- CNS disorder.
# Morphology of T waves
Shown below is an example of an ECG showing various morphologies of T wave.
## Shape
### Notched
- Notched in children and in adults with Pericarditis
### Differential diagnosis of the sharp, tented or pointed T wave
- Tall or "tented" symmetrical T waves may indicate hyperkalemia.
- One of the earliest electrocardiographic finding of acute myocardial infarction is sometimes the hyperacute T wave, which can be distinguished from hyperkalemia by the broad base and slight asymmetry.
- T waves can be sharply pointed in ischemia as well.
## Height
The T wave is normally not taller than > 5 mm in any standard lead and not taller than > 10 mm in any precordial lead.
### Differential diagnosis of the tall T wave:
- Hyperkalemia
- Left ventricular hypertrophy
- Myocardial Ischemia
- Myocardial infarction
- Ventricular strain
- Psychosis
- Cerebrovascular accident (usually inverted, widely splayed, frequently in subarrachnoid hemorrhages)
### Differential diagnosis of the short or flat T wave:
- Coronary ischemia
- Hypokalemia.
- Obesity. This finding may reverse with weight loss
# Significance of T-waves
Except in Hyperkalemia abnormality in T-wave alone is not diagnostic of any particular condition. Usually, T-wave abnormalities can provide added evidence to support clinical diagnosis.
# Cerebral T waves
## Overview
In 1954 George Burch described T wave abnormalities as myocardial ischemia mimics in patients with a variety of acute cerebral insults. His classic paper published in May 1954 popularized the term Cerebral T waves. The T waves were described as large, were similar to those seen in early myocardial isehemia, and were reported to revert to normal with improvement of the clinical condition, or changed to the pattern of any underlying heart disease present prior to the intracranial insult.
They usually appear as diffuse giant T-wave inversions or large, upright T-waves or sometimes as flat T-waves.
## Etiological Theories
Originally the cause was thought to be preexisting coronary artery disease exacerbated by the physiological demands of the critical illness. However in many cases, the autopsy studies of the heart showed no macroscopic evidence of significant coronary artery stenosis or myocardial infarction.
Hironosuke et al proposed widespread focal myocytolysis due to overstimulation of sympathetic centres in the hypothalamus leading to release of catecholamines which could damage myocardial cells
- By inducing constriction of the myocardial microcirculation, thus leading to focal ischemia or
- By a direct toxic effect
as the mechanism which result in the ECG changes seen in Subarachnoid hemorrhage.
After studying the characteristic pattern of focal myocardial lesions, some researchers proposed that the damaging catecholamines are released from intramyocardial nerve endings rather than from the general (systemic) circulation. This focal myocytolysis is different from myocardial infarction histologically and seems to have no prelidiction for subendocardial zone which is typical for myocardial infarction.
Rogers et al produced increases and decreases in the amplitude of the T wave in cats by stimulating the right and left sides of the hypothalamus and stellate ganglia respectively. They suggested that the mechanism is unilateral alteration of sympathetic tone to the heart.
Some studies proposed the ECG changes in acute cerebral events are due to the stimulation or injury to insular cortex which is proven to have cardiovascular effects on stimulation.
The suggestion that cerebral T waves are neurally induced is supported by the observation that inverted T waves may normalize if brain death occurs.
## Incidence and Prevalence
According to study on 150 acute stroke patients by David S Goldstein, T-wave inversions (Cerebral T-waves) were noticed in up to 29% of them.
In one case series, the ECG pattern of Cerebral T-waves with prolonged QT interval was seen in 72% of patients with subarachnoid hemorrhage and 57% of patients with intraparenchymal hemorrhage.
In a study of 100 consecutive patients with cerebrovascular accident(CVA), it is noted that there is 2 to 4 fold higher incidence of Cerebral T waves when compared to control group.
## New T wave abnormality, Cerebral or Cardiac???
In the acute setting, it is very significant to accurately interpret new T-wave changes to arrive at a diagnosis and provide timely intervention.
- History taking should include questions about past and present history of significant cardiovascular symptoms to rule out underlying heart disease. If any heart disease is present, the chances of it causing the abnormality should be considered.
- Quick correlation should be made with the rest of the ECG and clinical presentation of the patient.
- A quick neurological exam can be done to rule out cerebral origin of T-wave abnormality.
- In cases where neurological exam is not possible due to patient condition, QT interval should be evaluated. Usually in cerebral causes, there is associated prolonged QT interval versus normal QT interval seen in myocardial infarction.
However, to arrive at a definitive diagnosis, methods for diagnosing acute myocardial injury are necessary like
- Echocardiography
- Lab tests to detect elevated levels of biochemical markers of myocardial injury and
- Autopsy findings in case death occurs.
# Non-specific flipped T waves
Causes
- CAD/ischemia
- Cardiomyopathies
- Myocarditis, pericarditis
- PE
- Valvular disorders
- CNS bleed
- LVH, BBB, paced
Shown below is an example of an ECG showing non specific flipped T waves.
# Examples
Shown below is an example of an ECG demonstrating tall peaked T waves seen in hyperkalemia.
Shown below is an example of ECG showing tall peaked T waves (seen in hyperkalemia).
Shown below is an example of an ECG showing T wave inversions and appearance of U wave.
Shown below is an example of ECG showing hyperacute, asymmetrical and broad based T waves in anterior leads; also showing poor R wave progression
Shown below is an example of an ECG showing tall T waves in V1 seen in Left bundle branch block and left ventricular hypertrophy
Shown below is an EKG demonstrating typical negative T waves post anterior myocardial infarction. This patient also shows QTc prolongation. Whether this has an effect on prognosis is debated.
Copyleft image obtained courtesy of, Normal 0 false false false EN-US X-NONE X-NONE
# Sources
Copyleft images obtained - courtesy of ECGpedia, | T wave
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2] Prashanth Saddala M.B.B.S
# Overview
The T wave represents the repolarization (or recovery) of the ventricles. The interval from the beginning of the QRS complex to the apex of the T wave is referred to as the absolute refractory period. The last half of the T wave is referred to as the relative refractory period (or vulnerable period).
# Orientation of T waves
## Normal Orientation
### General
- Normally upright in leads 1 and 2 and in the chest leads over the left ventricle.
### Precordial Leads
- Lead V1 may have a positive, negative, or biphasic T wave.
- The T wave in V1 may be inverted at any age (is more often inverted than upright) and the T in V2 can normally be inverted.
- When the T in V1 is upright, it is almost never as tall as the T in V6.
- In infants and young children precordial T waves may be inverted.
- In adult males it is considered abnormal if the T waves are inverted as far to the left as lead V3.
- In adult females the T in V3 may be shallowly inverted.
### aVF
- Normally upright in aVL and aVF if the QRS is > 5 mm tall but may be inverted if the R waves are smaller.
- It is not uncommon to have an isolated negative T wave in lead III, aVL, or aVF. Cardiologists are often asked to consult pre-operativley on the patient with the isolated flipped T in lead III.
### aVR
- Normally inverted in aVR.
### In The Presence of Conduction Delay
- When a conduction abnormality (e.g., left bundle branch block,right bundle branch block, or a paced rhythm) is present, the T wave should be deflected opposite the terminal deflection of the QRS complex. This is known as appropriate T wave discordance. If the T waves are oriented in the same direction as the QRS complex, this is termed T wave concordance, and may be a sign of ischemia in the presence of left bundle branch block.
### Differential Diagnosis of Inverted or Negative T waves:
- Coronary ischemia
- Left ventricular hypertrophy
- CNS disorder.
# Morphology of T waves
Shown below is an example of an ECG showing various morphologies of T wave.
## Shape
### Notched
- Notched in children and in adults with Pericarditis
### Differential diagnosis of the sharp, tented or pointed T wave
- Tall or "tented" symmetrical T waves may indicate hyperkalemia.
- One of the earliest electrocardiographic finding of acute myocardial infarction is sometimes the hyperacute T wave, which can be distinguished from hyperkalemia by the broad base and slight asymmetry.
- T waves can be sharply pointed in ischemia as well.
## Height
The T wave is normally not taller than > 5 mm in any standard lead and not taller than > 10 mm in any precordial lead.
### Differential diagnosis of the tall T wave:
- Hyperkalemia
- Left ventricular hypertrophy
- Myocardial Ischemia
- Myocardial infarction
- Ventricular strain
- Psychosis
- Cerebrovascular accident (usually inverted, widely splayed, frequently in subarrachnoid hemorrhages)
### Differential diagnosis of the short or flat T wave:
- Coronary ischemia
- Hypokalemia.
- Obesity. This finding may reverse with weight loss
# Significance of T-waves
Except in Hyperkalemia abnormality in T-wave alone is not diagnostic of any particular condition. Usually, T-wave abnormalities can provide added evidence to support clinical diagnosis.[1]
# Cerebral T waves
## Overview
In 1954 George Burch described T wave abnormalities as myocardial ischemia mimics in patients with a variety of acute cerebral insults. His classic paper [2] published in May 1954 popularized the term Cerebral T waves. The T waves were described as large, were similar to those seen in early myocardial isehemia, and were reported to revert to normal with improvement of the clinical condition, or changed to the pattern of any underlying heart disease present prior to the intracranial insult.
They usually appear as diffuse giant T-wave inversions or large, upright T-waves or sometimes as flat T-waves.
## Etiological Theories
Originally the cause was thought to be preexisting coronary artery disease exacerbated by the physiological demands of the critical illness. However in many cases, the autopsy studies of the heart showed no macroscopic evidence of significant coronary artery stenosis or myocardial infarction.
Hironosuke et al[3] proposed widespread focal myocytolysis due to overstimulation of sympathetic centres in the hypothalamus leading to release of catecholamines which could damage myocardial cells
- By inducing constriction of the myocardial microcirculation, thus leading to focal ischemia or
- By a direct toxic effect
as the mechanism which result in the ECG changes seen in Subarachnoid hemorrhage.
After studying the characteristic pattern of focal myocardial lesions, some researchers proposed that the damaging catecholamines are released from intramyocardial nerve endings rather than from the general (systemic) circulation.[4] This focal myocytolysis is different from myocardial infarction histologically and seems to have no prelidiction for subendocardial zone which is typical for myocardial infarction. [3]
Rogers et al[5] produced increases and decreases in the amplitude of the T wave in cats by stimulating the right and left sides of the hypothalamus and stellate ganglia respectively. They suggested that the mechanism is unilateral alteration of sympathetic tone to the heart.
Some studies proposed the ECG changes in acute cerebral events are due to the stimulation or injury to insular cortex which is proven to have cardiovascular effects on stimulation.[6][7]
The suggestion that cerebral T waves are neurally induced is supported by the observation that inverted T waves may normalize if brain death occurs.
## Incidence and Prevalence
According to study on 150 acute stroke patients by David S Goldstein, T-wave inversions (Cerebral T-waves) were noticed in up to 29% of them.[8]
In one case series, the ECG pattern of Cerebral T-waves with prolonged QT interval was seen in 72% of patients with subarachnoid hemorrhage and 57% of patients with intraparenchymal hemorrhage.
In a study of 100 consecutive patients with cerebrovascular accident(CVA), it is noted that there is 2 to 4 fold higher incidence of Cerebral T waves when compared to control group.[9]
## New T wave abnormality, Cerebral or Cardiac???
In the acute setting, it is very significant to accurately interpret new T-wave changes to arrive at a diagnosis and provide timely intervention.
- History taking should include questions about past and present history of significant cardiovascular symptoms to rule out underlying heart disease. If any heart disease is present, the chances of it causing the abnormality should be considered.
- Quick correlation should be made with the rest of the ECG and clinical presentation of the patient.
- A quick neurological exam can be done to rule out cerebral origin of T-wave abnormality.
- In cases where neurological exam is not possible due to patient condition, QT interval should be evaluated. Usually in cerebral causes, there is associated prolonged QT interval versus normal QT interval seen in myocardial infarction.[1]
However, to arrive at a definitive diagnosis, methods for diagnosing acute myocardial injury are necessary like
- Echocardiography
- Lab tests to detect elevated levels of biochemical markers of myocardial injury and
- Autopsy findings in case death occurs.
# Non-specific flipped T waves
Causes
- CAD/ischemia
- Cardiomyopathies
- Myocarditis, pericarditis
- PE
- Valvular disorders
- CNS bleed
- LVH, BBB, paced[10]
Shown below is an example of an ECG showing non specific flipped T waves.
# Examples
Shown below is an example of an ECG demonstrating tall peaked T waves seen in hyperkalemia.
Shown below is an example of ECG showing tall peaked T waves (seen in hyperkalemia).
Shown below is an example of an ECG showing T wave inversions and appearance of U wave.
Shown below is an example of ECG showing hyperacute, asymmetrical and broad based T waves in anterior leads; also showing poor R wave progression
Shown below is an example of an ECG showing tall T waves in V1 seen in Left bundle branch block and left ventricular hypertrophy
Shown below is an EKG demonstrating typical negative T waves post anterior myocardial infarction. This patient also shows QTc prolongation. Whether this has an effect on prognosis is debated. [11][12][13]
Copyleft image obtained courtesy of, http://en.ecgpedia.org/wiki/Main_Page Normal 0 false false false EN-US X-NONE X-NONE
# Sources
Copyleft images obtained - courtesy of ECGpedia, [3] | https://www.wikidoc.org/index.php/T-wave | |
bdf05e82f69bc48b1b365494fac8d1206f63ffd3 | wikidoc | TADA2L | TADA2L
Transcriptional adapter 2-alpha is a protein that in humans is encoded by the TADA2A gene.
# Function
Many DNA-binding transcriptional activator proteins enhance the initiation rate of RNA polymerase II-mediated gene transcription by interacting functionally with the general transcription machinery bound at the basal promoter. Adaptor proteins are usually required for this activation, possibly to acetylate and destabilize nucleosomes, thereby relieving chromatin constraints at the promoter. The protein encoded by this gene is a transcriptional activator adaptor and has been found to be part of the PCAF histone acetylase complex. Two transcript variants encoding different isoforms have been identified for this gene.
# Interactions
TADA2L has been shown to interact with GCN5L2, TADA3L and Myc. | TADA2L
Transcriptional adapter 2-alpha is a protein that in humans is encoded by the TADA2A gene.[1][2]
# Function
Many DNA-binding transcriptional activator proteins enhance the initiation rate of RNA polymerase II-mediated gene transcription by interacting functionally with the general transcription machinery bound at the basal promoter. Adaptor proteins are usually required for this activation, possibly to acetylate and destabilize nucleosomes, thereby relieving chromatin constraints at the promoter. The protein encoded by this gene is a transcriptional activator adaptor and has been found to be part of the PCAF histone acetylase complex. Two transcript variants encoding different isoforms have been identified for this gene.[2]
# Interactions
TADA2L has been shown to interact with GCN5L2,[3][4] TADA3L[5][6] and Myc.[7] | https://www.wikidoc.org/index.php/TADA2L | |
c71d0190ab91639dbbb5828c87bf3cd57bf500b9 | wikidoc | TANGO2 | TANGO2
Transport and golgi organization 2 homolog (TANGO2) also known as chromosome 22 open reading frame 25 (C22orf25) is a protein that in humans is encoded by the TANGO2 gene.
The function of C22orf25 is not currently known. It is characterized by the NRDE superfamily domain (DUF883), which is strictly known for the conserved amino acid sequence of (N)-Asparagine (R)-Arginine (D)-Aspartic Acid (E)-Glutamic Acid. This domain is found among distantly related species from the six kingdoms: Eubacteria, Archaebacteria, Protista, Fungi, Plantae, and Animalia and is known to be involved in Golgi organization and protein secretion. It is likely that it localizes in the cytoplasm but is anchored in the cell membrane by the second amino acid. C22orf25 is also xenologous to T10 like proteins in the Fowlpox Virus and Canarypox Virus. The gene coding for C22orf25 is located on chromosome 22 and the location q11.21, so it is often associated with 22q11.2 deletion syndrome.
# Protein
# Gene neighborhood
The C22orf25 gene is located on the long arm (q) of chromosome 22 in region 1, band 1, and sub-band 2 (22q11.21) starting at 20,008,631 base pairs and ending at 20,053,447 base pairs. There is a 1.5-3.0 Mb deletion containing around 30-40 genes, spanning this region that causes the most survivable genetic deletion disorder known as 22q11.2 deletion syndrome, which is most commonly known as DiGeorge syndrome or Velocaridofacial syndrome. 22q11.2 deletion syndrome has a vast array of phenotypes and is not attributed to the loss of a single gene. The vast phenotypes arise from deletions of not only DiGeorge Syndrome Critical Region (DGCR) genes and disease genes but other unidentified genes as well.
C22orf25 is in close proximity to DGCR8 as well as other genes known to play a part in DiGeorge Syndrome such as armadillo repeat gene deleted in Velocardiofacial syndrome (ARVCF), Cathechol-O-methyltransferase (COMT) and T-box 1 (TBX1).
# Predicted mRNA features
## Promoter
The promoter for the C22orf25 gene spans 687 base pairs from 20,008,092 to 20,008,878 with a predicted transcriptional start site that is 104 base pairs and spans from 20,008,591 to 20,008,694. The promoter region and beginning of the C22orf25 gene (20,008,263 to 20,009,250) is not conserved past primates. This region was used to determine transcription factor interactions.
## Transcription factors
Some of the main transcription factors that bind to the promoter are listed below.
# Expression analysis
Expression data from Expressed Sequence Tag mapping, microarray and in situ hybridization show high expression for Homo sapiens in the blood, bone marrow and nerves. Expression is not restricted to these areas and low expression is seen elsewhere in the body. In Caenorhabditis elegans, the snt-1 gene (C22orf25 homologue) was expressed in the nerve ring, ventral and dorsal cord processes, sites of neuromuscular junctions, and in neurons.
# Evolutionary history
The NRDE (DUF883) domain, is a domain of unknown function spanning majority of the C22orf25 gene and is found among distantly related species, including viruses.
# Predicted protein features
## Post translational modifications
Post translational modifications of the C22orf25 gene that are evolutionarily conserved in the Animalia and Plantae kingdoms as well as the Canarypox Virus include glycosylation (C-mannosylation), glycation, phosphorylation (kinase specific), and palmitoylation.
## Predicted topology
C22orf25 localizes to the cytoplasm and is anchored to the cell membrane by the second amino acid. As mentioned previously, the second amino acid is modified by palmitoylation. Palmitoylation is known to contribute to membrane association because it contributes to enhanced hydrophobicity. Palmitoylation is known to play a role in the modulation of proteins' trafficking, stability and sorting. Palmitoylation is also involved in cellular signaling and neuronal transmission.
## Protein Interactions
C22orf25 has been shown to interact with NFKB1, RELA, RELB, BTRC, RPS27A, BCL3, MAP3K8, NFKBIA, SIN3A, SUMO1, Tat.
# Clinical significance
Mutations in the TANGO2 gene may cause defects in mitochondrial β-oxidation and increased endoplasmic reticulum stress and a reduction in Golgi volume density. These mutations results in early onset hypoglycemia, hyperammonemia, rhabdomyolysis, cardiac arrhythmias, and encephalopathy that later develops into cognitive impairment. | TANGO2
Transport and golgi organization 2 homolog (TANGO2) also known as chromosome 22 open reading frame 25 (C22orf25) is a protein that in humans is encoded by the TANGO2 gene.
The function of C22orf25 is not currently known. It is characterized by the NRDE superfamily domain (DUF883), which is strictly known for the conserved amino acid sequence of (N)-Asparagine (R)-Arginine (D)-Aspartic Acid (E)-Glutamic Acid. This domain is found among distantly related species from the six kingdoms:[1] Eubacteria, Archaebacteria, Protista, Fungi, Plantae, and Animalia and is known to be involved in Golgi organization and protein secretion.[2] It is likely that it localizes in the cytoplasm but is anchored in the cell membrane by the second amino acid.[3][4] C22orf25 is also xenologous to T10 like proteins in the Fowlpox Virus and Canarypox Virus. The gene coding for C22orf25 is located on chromosome 22 and the location q11.21, so it is often associated with 22q11.2 deletion syndrome.[5]
# Protein
# Gene neighborhood
The C22orf25 gene is located on the long arm (q) of chromosome 22 in region 1, band 1, and sub-band 2 (22q11.21) starting at 20,008,631 base pairs and ending at 20,053,447 base pairs.[5] There is a 1.5-3.0 Mb deletion containing around 30-40 genes, spanning this region that causes the most survivable genetic deletion disorder known as 22q11.2 deletion syndrome, which is most commonly known as DiGeorge syndrome or Velocaridofacial syndrome.[9][10] 22q11.2 deletion syndrome has a vast array of phenotypes and is not attributed to the loss of a single gene. The vast phenotypes arise from deletions of not only DiGeorge Syndrome Critical Region (DGCR) genes and disease genes but other unidentified genes as well.[11]
C22orf25 is in close proximity to DGCR8 as well as other genes known to play a part in DiGeorge Syndrome such as armadillo repeat gene deleted in Velocardiofacial syndrome (ARVCF), Cathechol-O-methyltransferase (COMT) and T-box 1 (TBX1).[12][13]
# Predicted mRNA features
## Promoter
The promoter for the C22orf25 gene spans 687 base pairs from 20,008,092 to 20,008,878 with a predicted transcriptional start site that is 104 base pairs and spans from 20,008,591 to 20,008,694.[14] The promoter region and beginning of the C22orf25 gene (20,008,263 to 20,009,250) is not conserved past primates. This region was used to determine transcription factor interactions.
## Transcription factors
Some of the main transcription factors that bind to the promoter are listed below.[15]
# Expression analysis
Expression data from Expressed Sequence Tag mapping, microarray and in situ hybridization show high expression for Homo sapiens in the blood, bone marrow and nerves.[16][17][18] Expression is not restricted to these areas and low expression is seen elsewhere in the body. In Caenorhabditis elegans, the snt-1 gene (C22orf25 homologue) was expressed in the nerve ring, ventral and dorsal cord processes, sites of neuromuscular junctions, and in neurons.[19]
# Evolutionary history
The NRDE (DUF883) domain, is a domain of unknown function spanning majority of the C22orf25 gene and is found among distantly related species, including viruses.
# Predicted protein features
## Post translational modifications
Post translational modifications of the C22orf25 gene that are evolutionarily conserved in the Animalia and Plantae kingdoms as well as the Canarypox Virus include glycosylation (C-mannosylation),[20] glycation,[21] phosphorylation (kinase specific),[22] and palmitoylation.[23]
## Predicted topology
C22orf25 localizes to the cytoplasm and is anchored to the cell membrane by the second amino acid. As mentioned previously, the second amino acid is modified by palmitoylation. Palmitoylation is known to contribute to membrane association[24] because it contributes to enhanced hydrophobicity.[3] Palmitoylation is known to play a role in the modulation of proteins' trafficking,[25] stability[26] and sorting.[27] Palmitoylation is also involved in cellular signaling[28] and neuronal transmission.[29]
## Protein Interactions
C22orf25 has been shown to interact with NFKB1,[30] RELA,[30] RELB,[30] BTRC,[30] RPS27A,[30] BCL3,[31] MAP3K8,[30] NFKBIA,[30] SIN3A,[30] SUMO1,[30] Tat.[32]
# Clinical significance
Mutations in the TANGO2 gene may cause defects in mitochondrial β-oxidation[33] and increased endoplasmic reticulum stress and a reduction in Golgi volume density.[34] These mutations results in early onset hypoglycemia, hyperammonemia, rhabdomyolysis, cardiac arrhythmias, and encephalopathy that later develops into cognitive impairment.[33][34] | https://www.wikidoc.org/index.php/TANGO2 | |
12321a467b49acaf0316e8ac7a9326c4d2aefe9b | wikidoc | TARBP2 | TARBP2
RISC-loading complex subunit TARBP2 is a protein that in humans is encoded by the TARBP2 gene.
# Function
HIV-1, the causative agent of acquired immunodeficiency syndrome (AIDS), contains an RNA genome that produces a chromosomally integrated DNA during the replicative cycle. Activation of HIV-1 gene expression by the transactivator Tat is dependent on an RNA regulatory element (TAR) located downstream of the transcription initiation site. The protein encoded by this gene binds between the bulge and the loop of the HIV-1 TAR RNA regulatory element and activates HIV-1 gene expression in synergy with the viral Tat protein. Alternative splicing results in multiple transcript variants encoding different isoforms. This gene also has a pseudogene.
# Interactions
TARBP2 has been shown to interact with Protein kinase R and RBM14. | TARBP2
RISC-loading complex subunit TARBP2 is a protein that in humans is encoded by the TARBP2 gene.[1][2]
# Function
HIV-1, the causative agent of acquired immunodeficiency syndrome (AIDS), contains an RNA genome that produces a chromosomally integrated DNA during the replicative cycle. Activation of HIV-1 gene expression by the transactivator Tat is dependent on an RNA regulatory element (TAR) located downstream of the transcription initiation site. The protein encoded by this gene binds between the bulge and the loop of the HIV-1 TAR RNA regulatory element and activates HIV-1 gene expression in synergy with the viral Tat protein. Alternative splicing results in multiple transcript variants encoding different isoforms. This gene also has a pseudogene.[2]
# Interactions
TARBP2 has been shown to interact with Protein kinase R[3][4] and RBM14.[5] | https://www.wikidoc.org/index.php/TARBP2 | |
59f054313064ac9311a02013a56aad4c1021d722 | wikidoc | TARDBP | TARDBP
TAR DNA-binding protein 43 (TDP-43, transactive response DNA binding protein 43 kDa), is a protein that in humans is encoded by the TARDBP gene.
# Function
TDP-43 is a transcriptional repressor that binds to chromosomally integrated TAR DNA and represses HIV-1 transcription. In addition, this protein regulates alternate splicing of the CFTR gene. In particular, TDP-43 is a splicing factor binding to the intron8/exon9 junction of the CFTR gene and to the intron2/exon3 region of the apoA-II gene. A similar pseudogene is present on chromosome 20.
TDP-43 has been shown to bind both DNA and RNA and have multiple functions in transcriptional repression, pre-mRNA splicing and translational regulation. Recent work has characterized the transcriptome-wide binding sites revealing that thousands of RNAs are bound by TDP-43 in neurons.
TDP-43 was originally identified as a transcriptional repressor that binds to chromosomally integrated trans-activation response element (TAR) DNA and represses HIV-1 transcription. It was also reported to regulate alternate splicing of the CFTR gene and the apoA-II gene.
In spinal motor neurons TDP-43 has also been shown in humans to be a low molecular weight neurofilament (hNFL) mRNA-binding protein. It has also shown to be a neuronal activity response factor in the dendrites of hippocampal neurons suggesting possible roles in regulating mRNA stability, transport and local translation in neurons.
Recently, it has been demonstrated that zinc ions are able to induce aggregation of endogenous TDP-43 in cells. Moreover, zinc could bind to RNA binding domain of TDP-43 and induce the formation of amyloid-like aggregates in vitro.
# Clinical significance
A hyper-phosphorylated, ubiquitinated and cleaved form of TDP-43—known as pathologic TDP43—is the major disease protein in ubiquitin-positive, tau-, and alpha-synuclein-negative frontotemporal dementia (FTLD-TDP, previously referred to as FTLD-U) and in amyotrophic lateral sclerosis (ALS). Elevated levels of the TDP-43 protein have also been identified in individuals diagnosed with chronic traumatic encephalopathy, a condition that often mimics ALS and that has been associated with athletes who have experienced multiple concussions and other types of head injury. Abnormalities of TDP-43 also occur in an important subset of Alzheimer's disease patients, correlating with clinical and neuropathologic features indexes.
HIV-1, the causative agent of acquired immunodeficiency syndrome (AIDS), contains an RNA genome that produces a chromosomally integrated DNA during the replicative cycle. Activation of HIV-1 gene expression by the transactivator "Tat" is dependent on an RNA regulatory element (TAR) located "downstream" (i.e. to-be transcribed at a later point in time) of the transcription initiation site.
Mutations in the TARDBP gene are associated with neurodegenerative disorders including frontotemporal lobar degeneration and amyotrophic lateral sclerosis (ALS). In particular, the TDP-43 mutants M337V and Q331K are being studied for their roles in ALS. Cytoplasmic TDP-43 pathology is the dominant histopathological feature of multisystem proteinopathy. The N-terminal domain, which contributes importantly to the aggregation of the C-terminal region, has a novel structure with two negatively charged loops. | TARDBP
TAR DNA-binding protein 43 (TDP-43, transactive response DNA binding protein 43 kDa), is a protein that in humans is encoded by the TARDBP gene.[1]
# Function
TDP-43 is a transcriptional repressor that binds to chromosomally integrated TAR DNA and represses HIV-1 transcription. In addition, this protein regulates alternate splicing of the CFTR gene. In particular, TDP-43 is a splicing factor binding to the intron8/exon9 junction of the CFTR gene and to the intron2/exon3 region of the apoA-II gene.[2] A similar pseudogene is present on chromosome 20.[3]
TDP-43 has been shown to bind both DNA and RNA and have multiple functions in transcriptional repression, pre-mRNA splicing and translational regulation. Recent work has characterized the transcriptome-wide binding sites revealing that thousands of RNAs are bound by TDP-43 in neurons.[4]
TDP-43 was originally identified as a transcriptional repressor that binds to chromosomally integrated trans-activation response element (TAR) DNA and represses HIV-1 transcription.[1] It was also reported to regulate alternate splicing of the CFTR gene and the apoA-II gene.
In spinal motor neurons TDP-43 has also been shown in humans to be a low molecular weight neurofilament (hNFL) mRNA-binding protein.[5] It has also shown to be a neuronal activity response factor in the dendrites of hippocampal neurons suggesting possible roles in regulating mRNA stability, transport and local translation in neurons.[6]
Recently, it has been demonstrated that zinc ions are able to induce aggregation of endogenous TDP-43 in cells.[7] Moreover, zinc could bind to RNA binding domain of TDP-43 and induce the formation of amyloid-like aggregates in vitro.[8]
# Clinical significance
A hyper-phosphorylated, ubiquitinated and cleaved form of TDP-43—known as pathologic TDP43—is the major disease protein in ubiquitin-positive, tau-, and alpha-synuclein-negative frontotemporal dementia (FTLD-TDP, previously referred to as FTLD-U[9]) and in amyotrophic lateral sclerosis (ALS).[10][11] Elevated levels of the TDP-43 protein have also been identified in individuals diagnosed with chronic traumatic encephalopathy, a condition that often mimics ALS and that has been associated with athletes who have experienced multiple concussions and other types of head injury.[12] Abnormalities of TDP-43 also occur in an important subset of Alzheimer's disease patients, correlating with clinical and neuropathologic features indexes.[13]
HIV-1, the causative agent of acquired immunodeficiency syndrome (AIDS), contains an RNA genome that produces a chromosomally integrated DNA during the replicative cycle. Activation of HIV-1 gene expression by the transactivator "Tat" is dependent on an RNA regulatory element (TAR) located "downstream" (i.e. to-be transcribed at a later point in time) of the transcription initiation site.
Mutations in the TARDBP gene are associated with neurodegenerative disorders including frontotemporal lobar degeneration and amyotrophic lateral sclerosis (ALS).[14] In particular, the TDP-43 mutants M337V and Q331K are being studied for their roles in ALS.[15][16] Cytoplasmic TDP-43 pathology is the dominant histopathological feature of multisystem proteinopathy.[17] The N-terminal domain, which contributes importantly to the aggregation of the C-terminal region, has a novel structure with two negatively charged loops.[18] | https://www.wikidoc.org/index.php/TARDBP | |
dc307fc7f03499c0361585949cc8851e5efc3552 | wikidoc | TAS1R1 | TAS1R1
Taste receptor type 1 member 1 is a protein that in humans is encoded by the TAS1R1 gene.
# Structure
The protein encoded by the TAS1R1 gene is a G protein-coupled receptor with seven trans-membrane domains and is a component of the heterodimeric amino acid taste receptor T1R1+3. This receptor is formed as a dimer of the TAS1R1 and TAS1R3 proteins. Moreover, the TAS1R1 protein is not functional outside of formation of the 1+3 heterodimer. The TAS1R1+3 receptor has been shown to respond to L-amino acids but not to their D-enantiomers or other compounds. This ability to bind L-amino acids, specifically L-glutamine, enables the body to sense the umami, or savory, taste. Multiple transcript variants encoding several different isoforms have been found for this gene, which may account for differing taste thresholds among individuals for the umami taste. Another interesting quality of the TAS1R1 and TAS1R2 proteins is their spontaneous activity in the absence of the extracellular domains and binding ligands. This may mean that the extracellular domain regulates function of the receptor by preventing spontaneous action as well as binding to activating ligands such as L-glutamine.
# Ligands
The umami taste is distinctly related to the compound monosodium glutamate(MSG). Synthesized in 1908 by Japanese chemist Kikunae Ikeda, this flavor-enhancing compound led to the naming of a new flavor quality that was named “umami”, the Japanese word for “tasty”. The TAS1R1+3 taste receptor is sensitive to the glutamate in MSG as well as the synergistic taste-enhancer molecules inosine monophosphate (IMP) and guanosine monophosphate (GMP). These taste-enhancer molecules are unable to activate the receptor alone, but are rather used to enhance receptor responses to many L-amino acids.
# Signal transduction
TAS1R1 and TAS1R2 receptors have been shown to bind to G proteins, most often the gustducin Gα subunit, although a gustducin knock-out has shown small residual activity. TAS1R1 and TAS1R2 have also been shown to activate Gαo and Gαi. This suggests that TAS1R1 and TAS1R2 are G protein-coupled receptors that inhibit adenylyl cyclases to decrease cyclic guanosine monophosphate (cGMP) levels in taste receptors.
Research done by creating knock-outs of common channels activated by sensory G-protein second messenger systems has also shown a connection between umami taste perception and the phosphatidylinositol (PIP2) pathway. The nonselecive cation Transient Receptor Potential channel TRPM5 has been shown to correlate with both umami and sweet taste. Also, the phospholipase PLCβ2 was shown to similarly correlate with umami and sweet taste. This suggests that activation of the G-protein pathway and subsequent activation of PLC β2 and the TRPM5 channel in these taste cells functions to activate the cell.
# Location and innervation
TAS1R1+3 expressing cells are found mostly in the fungiform papillae at the tip and edges of the tongue and palate taste receptor cells in the roof of the mouth. These cells are shown to synapse upon the chorda tympani nerves to send their signals to the brain, although some activation of the glossopharyngeal nerve has been found. TAS1R and TAS2R (bitter) channels are not expressed together in taste buds. | TAS1R1
Taste receptor type 1 member 1 is a protein that in humans is encoded by the TAS1R1 gene.[1]
# Structure
The protein encoded by the TAS1R1 gene is a G protein-coupled receptor with seven trans-membrane domains and is a component of the heterodimeric amino acid taste receptor T1R1+3. This receptor is formed as a dimer of the TAS1R1 and TAS1R3 proteins. Moreover, the TAS1R1 protein is not functional outside of formation of the 1+3 heterodimer.[2] The TAS1R1+3 receptor has been shown to respond to L-amino acids but not to their D-enantiomers or other compounds. This ability to bind L-amino acids, specifically L-glutamine, enables the body to sense the umami, or savory, taste.[3] Multiple transcript variants encoding several different isoforms have been found for this gene, which may account for differing taste thresholds among individuals for the umami taste.[1][4] Another interesting quality of the TAS1R1 and TAS1R2 proteins is their spontaneous activity in the absence of the extracellular domains and binding ligands.[5] This may mean that the extracellular domain regulates function of the receptor by preventing spontaneous action as well as binding to activating ligands such as L-glutamine.
# Ligands
The umami taste is distinctly related to the compound monosodium glutamate(MSG). Synthesized in 1908 by Japanese chemist Kikunae Ikeda, this flavor-enhancing compound led to the naming of a new flavor quality that was named “umami”, the Japanese word for “tasty”.[6] The TAS1R1+3 taste receptor is sensitive to the glutamate in MSG as well as the synergistic taste-enhancer molecules inosine monophosphate (IMP) and guanosine monophosphate (GMP). These taste-enhancer molecules are unable to activate the receptor alone, but are rather used to enhance receptor responses to many L-amino acids.[3][7]
# Signal transduction
TAS1R1 and TAS1R2 receptors have been shown to bind to G proteins, most often the gustducin Gα subunit, although a gustducin knock-out has shown small residual activity. TAS1R1 and TAS1R2 have also been shown to activate Gαo and Gαi.[5] This suggests that TAS1R1 and TAS1R2 are G protein-coupled receptors that inhibit adenylyl cyclases to decrease cyclic guanosine monophosphate (cGMP) levels in taste receptors.[8]
Research done by creating knock-outs of common channels activated by sensory G-protein second messenger systems has also shown a connection between umami taste perception and the phosphatidylinositol (PIP2) pathway. The nonselecive cation Transient Receptor Potential channel TRPM5 has been shown to correlate with both umami and sweet taste. Also, the phospholipase PLCβ2 was shown to similarly correlate with umami and sweet taste. This suggests that activation of the G-protein pathway and subsequent activation of PLC β2 and the TRPM5 channel in these taste cells functions to activate the cell.[9]
# Location and innervation
TAS1R1+3 expressing cells are found mostly in the fungiform papillae at the tip and edges of the tongue and palate taste receptor cells in the roof of the mouth.[2] These cells are shown to synapse upon the chorda tympani nerves to send their signals to the brain, although some activation of the glossopharyngeal nerve has been found.[3][10] TAS1R and TAS2R (bitter) channels are not expressed together in taste buds.[2] | https://www.wikidoc.org/index.php/TAS1R1 | |
7879c91d898f1f6feb7e5737b4360be345382d45 | wikidoc | TAS1R2 | TAS1R2
Taste receptor type 1 member 2 is a protein that in humans is encoded by the TAS1R2 gene.
# Structure
The protein encoded by the TAS1R2 gene is a G protein-coupled receptor with seven trans-membrane domains and is a component of the heterodimeric amino acid taste receptor T1R2+3. This receptor is formed as a dimer of the TAS1R2 and TAS1R3 proteins. Moreover, the TAS1R2 protein is not functional without formation of the 2+3 heterodimer.
Another interesting quality of the TAS1R2 and TAS1R1 genes is their spontaneous activity in the absence of the extracellular domains and binding ligands. This may mean that the extracellular domain regulates function of the receptor by preventing spontaneous action as well as binding to activating ligands such as sucrose.
# Ligands
The TAS1R2+3 receptor has been shown to respond to natural sugars sucrose and fructose, and to the artificial sweeteners saccharin, acesulfame potassium, dulcin, and guanidinoacetic acid. Research initially suggested that rat receptors did not respond to many other natural and artificial sugars, such as glucose and aspartame, leading to the conclusion that there must be more than one type of sweet taste receptor. Contradictory evidence, however, suggested that cells expressing the human TAS1R2+3 receptor showed sensitivity to both aspartame and glucose but cells expressing the rat TAS1R2+3 receptor were only slightly activated by glucose and showed no aspartame activation. These results are inconclusive about the existence of another sweet taste receptor, but show that the TAS1R2+3 receptors are responsible for a wide variety of different sweet tastes.
# Signal transduction
TAS1R2 and TAS1R1 receptors have been shown to bind to G proteins, most often the gustducin Gα subunit, although a gusducin knock-out has shown small residual activity. TAS1R2 and TAS1R1 have also been shown to activate Gαo and Gαi protein subunits. This suggests that TAS1R1 and TAS1R2 are G protein-coupled receptors that inhibit adenylyl cyclases to decrease cyclic guanosine monophosphate (cGMP) levels in taste receptors.
Research done by creating knock-outs of common channels activated by sensory G-protein second messenger systems has also shown a connection between sweet taste perception and the phosphatidylinositol (PIP2) pathway. The nonselecive cation Transient Receptor Potential channel TRPM5 has been shown to correlate with both umami and sweet taste. Also, the phospholipase PLCβ2 was shown to similarly correlate with umami and sweet taste. This suggests that activation of the G-protein pathway and subsequent activation of PLC β2 and the TRPM5 channel in these taste cells functions to activate the cell.
# Location and innervation
TAS1R2+3 expressing cells are found in circumvallate papillae and foliate papillae near the back of the tongue and palate taste receptor cells in the roof of the mouth. These cells are shown to synapse upon the chorda tympani and glossopharyngeal nerves to send their signals to the brain.
TAS1R and TAS2R (bitter) channels are not expressed together in taste buds. | TAS1R2
Taste receptor type 1 member 2 is a protein that in humans is encoded by the TAS1R2 gene.[1]
# Structure
The protein encoded by the TAS1R2 gene is a G protein-coupled receptor with seven trans-membrane domains and is a component of the heterodimeric amino acid taste receptor T1R2+3. This receptor is formed as a dimer of the TAS1R2 and TAS1R3 proteins. Moreover, the TAS1R2 protein is not functional without formation of the 2+3 heterodimer.[2]
Another interesting quality of the TAS1R2 and TAS1R1 genes is their spontaneous activity in the absence of the extracellular domains and binding ligands.[3] This may mean that the extracellular domain regulates function of the receptor by preventing spontaneous action as well as binding to activating ligands such as sucrose.
# Ligands
The TAS1R2+3 receptor has been shown to respond to natural sugars sucrose and fructose, and to the artificial sweeteners saccharin, acesulfame potassium, dulcin, and guanidinoacetic acid. Research initially suggested that rat receptors did not respond to many other natural and artificial sugars, such as glucose and aspartame, leading to the conclusion that there must be more than one type of sweet taste receptor.[2] Contradictory evidence, however, suggested that cells expressing the human TAS1R2+3 receptor showed sensitivity to both aspartame and glucose but cells expressing the rat TAS1R2+3 receptor were only slightly activated by glucose and showed no aspartame activation.[4] These results are inconclusive about the existence of another sweet taste receptor, but show that the TAS1R2+3 receptors are responsible for a wide variety of different sweet tastes.
# Signal transduction
TAS1R2 and TAS1R1 receptors have been shown to bind to G proteins, most often the gustducin Gα subunit, although a gusducin knock-out has shown small residual activity. TAS1R2 and TAS1R1 have also been shown to activate Gαo and Gαi protein subunits.[3] This suggests that TAS1R1 and TAS1R2 are G protein-coupled receptors that inhibit adenylyl cyclases to decrease cyclic guanosine monophosphate (cGMP) levels in taste receptors.[5]
Research done by creating knock-outs of common channels activated by sensory G-protein second messenger systems has also shown a connection between sweet taste perception and the phosphatidylinositol (PIP2) pathway. The nonselecive cation Transient Receptor Potential channel TRPM5 has been shown to correlate with both umami and sweet taste. Also, the phospholipase PLCβ2 was shown to similarly correlate with umami and sweet taste. This suggests that activation of the G-protein pathway and subsequent activation of PLC β2 and the TRPM5 channel in these taste cells functions to activate the cell.[6]
# Location and innervation
TAS1R2+3 expressing cells are found in circumvallate papillae and foliate papillae near the back of the tongue and palate taste receptor cells in the roof of the mouth.[2] These cells are shown to synapse upon the chorda tympani and glossopharyngeal nerves to send their signals to the brain.[7][8]
TAS1R and TAS2R (bitter) channels are not expressed together in taste buds.[2] | https://www.wikidoc.org/index.php/TAS1R2 | |
932793bf13e46aafe900980fd6315013c80748fb | wikidoc | TAS1R3 | TAS1R3
Taste receptor type 1 member 3 is a protein that in humans is encoded by the TAS1R3 gene. The TAS1R3 gene encodes the human homolog of mouse Sac taste receptor, a major determinant of differences between sweet-sensitive and -insensitive mouse strains in their responsiveness to sucrose, saccharin, and other sweeteners.
# Structure
The protein encoded by the TAS1R3 gene is a G protein-coupled receptor with seven trans-membrane domains and is a component of the heterodimeric amino acid taste receptor TAS1R1+3 and sweet taste receptor TAS1R2+3. This receptor is formed as a protein dimer with either TAS1R1 or TAS1R2.
Experiments have also shown that a homo-dimer of TAS1R3 is also sensitive to natural sugar substances. This has been hypothesized as the mechanism by which sugar substitutes do not have the same taste qualities as natural sugars.
# Ligands
The G protein-coupled receptors for sweet and umami taste are formed by dimers of the TAS1R proteins.
The TAS1R1+3 taste receptor is sensitive to the glutamate in MSG as well as the synergistic taste-enhancer molecules inosine monophosphate (IMP) and guanosine monophosphate (GMP). These taste-enhancer molecules are unable to activate the receptor alone, but are rather used to enhance receptor responses many to L-amino acids. The TAS1R2+3 receptor has been shown to respond to natural sugars sucrose and fructose, and to artificial sweeteners saccharin, acesulfame potassium, dulcin, guanidinoacetic acid.
# Signal transduction
TAS1R2 and TAS1R1 receptors have been shown to bind to G proteins, most often the gustducin Gα subunit, although a gusducin knock-out has shown small residual activity. TAS1R2 and TAS1R1 have also been shown to activate Gαo and Gαi protein subunits. This suggests that TAS1R1 and TAS1R2 are G protein-coupled receptors that inhibit adenylyl cyclases to decrease cyclic guanosine monophosphate (cGMP) levels in taste receptors. The TAS1R3 protein, however, has been shown in vitro to couple with Gα subunits at a much lower rate than the other TAS1R proteins. While the protein structures of the TAS1R proteins are similar, this experiment shows that the G protein-coupling properties of TAS1R3 may be less important in the transduction of taste signals than the TAS1R1 and TAS1R2 proteins.
# Location and innervation
TAS1R1+3 expressing cells are found in fungiform papillae at the tip and edges of the tongue and palate taste receptor cells in the roof of the mouth. These cells are shown to synapse upon the chorda tympani nerves to send their signals to the brain. TAS1R2+3 expressing cells are found in circumvallate papillae and foliate papillae near the back of the tongue and palate taste receptor cells in the roof of the mouth. These cells are shown to synapse upon the glossopharyngeal nerves to send their signals to the brain. TAS1R and TAS2R (bitter) channels are not expressed together in any taste buds. | TAS1R3
Taste receptor type 1 member 3 is a protein that in humans is encoded by the TAS1R3 gene.[1][2] The TAS1R3 gene encodes the human homolog of mouse Sac taste receptor, a major determinant of differences between sweet-sensitive and -insensitive mouse strains in their responsiveness to sucrose, saccharin, and other sweeteners.[2][3]
# Structure
The protein encoded by the TAS1R3 gene is a G protein-coupled receptor with seven trans-membrane domains and is a component of the heterodimeric amino acid taste receptor TAS1R1+3 and sweet taste receptor TAS1R2+3. This receptor is formed as a protein dimer with either TAS1R1 or TAS1R2.[4]
Experiments have also shown that a homo-dimer of TAS1R3 is also sensitive to natural sugar substances. This has been hypothesized as the mechanism by which sugar substitutes do not have the same taste qualities as natural sugars.[5]
# Ligands
The G protein-coupled receptors for sweet and umami taste are formed by dimers of the TAS1R proteins.
The TAS1R1+3 taste receptor is sensitive to the glutamate in MSG as well as the synergistic taste-enhancer molecules inosine monophosphate (IMP) and guanosine monophosphate (GMP). These taste-enhancer molecules are unable to activate the receptor alone, but are rather used to enhance receptor responses many to L-amino acids.[6] The TAS1R2+3 receptor has been shown to respond to natural sugars sucrose and fructose, and to artificial sweeteners saccharin, acesulfame potassium, dulcin, guanidinoacetic acid.[4]
# Signal transduction
TAS1R2 and TAS1R1 receptors have been shown to bind to G proteins, most often the gustducin Gα subunit, although a gusducin knock-out has shown small residual activity. TAS1R2 and TAS1R1 have also been shown to activate Gαo and Gαi protein subunits.[7] This suggests that TAS1R1 and TAS1R2 are G protein-coupled receptors that inhibit adenylyl cyclases to decrease cyclic guanosine monophosphate (cGMP) levels in taste receptors.[8] The TAS1R3 protein, however, has been shown in vitro to couple with Gα subunits at a much lower rate than the other TAS1R proteins. While the protein structures of the TAS1R proteins are similar, this experiment shows that the G protein-coupling properties of TAS1R3 may be less important in the transduction of taste signals than the TAS1R1 and TAS1R2 proteins.[7]
# Location and innervation
TAS1R1+3 expressing cells are found in fungiform papillae at the tip and edges of the tongue and palate taste receptor cells in the roof of the mouth.[4] These cells are shown to synapse upon the chorda tympani nerves to send their signals to the brain.[6] TAS1R2+3 expressing cells are found in circumvallate papillae and foliate papillae near the back of the tongue and palate taste receptor cells in the roof of the mouth.[4] These cells are shown to synapse upon the glossopharyngeal nerves to send their signals to the brain.[9][10] TAS1R and TAS2R (bitter) channels are not expressed together in any taste buds.[4] | https://www.wikidoc.org/index.php/TAS1R3 | |
5e883b02cec3d9a1eb83eb15068e3d47aee762ab | wikidoc | TAS2R9 | TAS2R9
Taste receptor type 2 member 9 is a protein that in humans is encoded by the TAS2R9 gene.
# Function
This gene product belongs to the family of candidate taste receptors that are members of the G-protein-coupled receptor superfamily. These proteins are specifically expressed in the taste receptor cells of the tongue and palate epithelia. They are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. In functional expression studies, they respond to bitter tastants. This gene maps to the taste receptor gene cluster on chromosome 12p13.
Polymorphisms in this gene have been associated with the perceived bitterness of sweetener acesulfame potassium. | TAS2R9
Taste receptor type 2 member 9 is a protein that in humans is encoded by the TAS2R9 gene.[1][2][3]
# Function
This gene product belongs to the family of candidate taste receptors that are members of the G-protein-coupled receptor superfamily. These proteins are specifically expressed in the taste receptor cells of the tongue and palate epithelia. They are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. In functional expression studies, they respond to bitter tastants. This gene maps to the taste receptor gene cluster on chromosome 12p13.[3]
Polymorphisms in this gene have been associated with the perceived bitterness of sweetener acesulfame potassium.[4] | https://www.wikidoc.org/index.php/TAS2R9 | |
4c29beaa5c30e370aaaa029e866047c99ba6785a | wikidoc | TBC1D4 | TBC1D4
AS160 (Akt substrate of 160 kDa), which was originally known as TBC1 domain family member 4 (TBC1D4), is a Rab GTPase-activating protein that in humans is encoded by the TBC1D4 gene.
The 160 kD protein product was first discovered in a screen for novel substrates of the serine-threonine kinase Akt2, which phosphorylates AS160 at Thr-642 and Ser-588 after insulin stimulation. Insulin stimulation of fat and muscle cells results in translocation of the glucose transporter GLUT4 to the plasma membrane, and this translocation process is dependent on phosphorylation of AS160. The role of AS160 in GLUT4 translocation is mediated by its GTPase activating domain and interactions with Rab proteins in vesicle formation, increasing GLUT4 translocation when its GTPase activity is inhibited by Akt phosphorylation. Specifically, this inhibition activates RAB2A, RAB8A, RAB10 and RAB14.
AS160 also contains a calmodulin-binding domain, and this domain mediates phosphorylation-independent glucose uptake in muscle cells. | TBC1D4
AS160 (Akt substrate of 160 kDa), which was originally known as TBC1 domain family member 4 (TBC1D4),[1] is a Rab GTPase-activating protein that in humans is encoded by the TBC1D4 gene.[2][3][4][5]
The 160 kD protein product was first discovered in a screen for novel substrates of the serine-threonine kinase Akt2, which phosphorylates AS160 at Thr-642 and Ser-588[1][6] after insulin stimulation.[7] Insulin stimulation of fat and muscle cells results in translocation of the glucose transporter GLUT4 to the plasma membrane, and this translocation process is dependent on phosphorylation of AS160.[8] The role of AS160 in GLUT4 translocation is mediated by its GTPase activating domain and interactions with Rab proteins in vesicle formation, increasing GLUT4 translocation when its GTPase activity is inhibited by Akt phosphorylation. Specifically, this inhibition activates RAB2A, RAB8A, RAB10 and RAB14.[9]
AS160 also contains a calmodulin-binding domain, and this domain mediates phosphorylation-independent glucose uptake in muscle cells.[10] | https://www.wikidoc.org/index.php/TBC1D4 | |
8ac73714442f2d4876b3b65d5e3a4dced7597340 | wikidoc | TCF7L1 | TCF7L1
Transcription factor 7-like 1 (T-cell specific, HMG-box), also known as TCF7L1, is a human gene.
This gene encodes a member of the T cell factor/lymphoid enhancer factor family of transcription factors. These transcription factors are activated by beta catenin, mediate the Wnt signaling pathway and are antagonized by the transforming growth factor beta signaling pathway. The encoded protein contains a high mobility group-box DNA binding domain and participates in the regulation of cell cycle genes and cellular senescence.
# Model organisms
Model organisms have been used in the study of TCF7L1 function. A conditional knockout mouse line, called Tcf7l1tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty four tests were carried out on mutant mice and two significant abnormalities were observed. Few homozygous mutant embryos were identified during gestation, and those that did survive had a severe craniofacial defect. None survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no additional significant abnormalities were observed in these animals. | TCF7L1
Transcription factor 7-like 1 (T-cell specific, HMG-box), also known as TCF7L1, is a human gene.[1]
This gene encodes a member of the T cell factor/lymphoid enhancer factor family of transcription factors. These transcription factors are activated by beta catenin, mediate the Wnt signaling pathway and are antagonized by the transforming growth factor beta signaling pathway. The encoded protein contains a high mobility group-box DNA binding domain and participates in the regulation of cell cycle genes and cellular senescence.[1]
# Model organisms
Model organisms have been used in the study of TCF7L1 function. A conditional knockout mouse line, called Tcf7l1tm1a(EUCOMM)Wtsi[6][7] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[8][9][10]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[4][11] Twenty four tests were carried out on mutant mice and two significant abnormalities were observed.[4] Few homozygous mutant embryos were identified during gestation, and those that did survive had a severe craniofacial defect. None survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no additional significant abnormalities were observed in these animals.[4] | https://www.wikidoc.org/index.php/TCF7L1 | |
e283dcaf0f751d93061151ec3cff39fcd58ae129 | wikidoc | TCF7L2 | TCF7L2
Transcription factor 7-like 2 (T-cell specific, HMG-box) also known as TCF7L2 or TCF4 is a protein acting as a transcription factor that in humans, is encoded by the TCF7L2 gene. The TCF7L2 gene is located on chromosome 10q25.2-q25.3, contains 19 exons, and has autosomal dominant inheritance. The TCF7L2 gene is polymorphic and pleiotropic. As a member of the TCF family, TCF7L2 can form a bipartite transcription factor and influence several biological pathways, including the Wnt signalling pathway. The single nucleotide polymorphism (SNP) within the TCF7L2 gene, rs7903146, is, to date, the most significant genetic marker associated with Type 2 diabetes mellitus (T2DM) risk. SNPs in this gene are especially known to be linked to higher risk to develop type 2 diabetes, gestational diabetes, and multiple other diseases.
# Function
TCF7L2 is a transcription factor influencing the transcription of several genes thereby exerting a large variety of functions within the cell. It is a member of the TCF family that can form a bipartite transcription factor (β-catenin/TCF) alongside β-catenin. Bipartite transcription factors can have large effects on the Wnt signalling pathway. Stimulation of the Wnt signaling pathway leads to the association of β-catenin with BCL9, translocation to the nucleus, and association with TCF7L2, which in turn results in the activation of Wnt target genes. The activation of the Wnt target genes specifically represses proglucagon synthesis in enteroendocrine cells. The repression of TCF7L2 using HMG-box repressor (HBP1) inhibits Wnt signalling. Therefore, TCF7L2 is an effector in the Wnt signalling pathway. TCF7L2's role in glucose metabolism is expressed in many tissues such as gut, brain, liver, and skeletal muscle. However, TCF7L2 does not directly regulate glucose metabolism in β-cells, but regulates glucose metabolism in pancreatic and liver tissues.
The TCF7L2 gene encoding the TCF7L2 transcription factor, exhibits multiple functions through its polymorphisms and thus, is known as a pleiotropic gene. Type 2 diabetes T2DM susceptibility is exhibited in carriers of TCF7L2 rs7903146C>T and rs290481T>C polymorphisms. TCF7L2 rs290481T>C polymorphism, however, has shown no significant correlation to the susceptibility to gestational diabetes mellitus (GDM) in a Chinese Han population, whereas the T alleles of rs7903146 and rs1799884 increase susceptibility to GDM in the Chinese Han population. The difference in effects of the different polymorphisms of the gene indicate that the gene is indeed pleiotropic.
# Structure
The TCF7L2 gene, encoding the TCF7L2 protein, is located on chromosome 10q25.2-q25.3. The gene contains 19 exons and has autosomal dominant inheritance. Of the 19 exons, 5 are alternative. The TCF7L2 gene contains 619 amino acids and its molecular mass is 67919 Da. TCF7L2's secondary structure is a helix-turn-helix structure.
# Tissue Distribution
TCF7L2 does not primarily operate in the β-cells in the pancreas. It is also expressed in brain, liver, intestine, and fat cells.
# Clinical significance
## Type 2 Diabetes
Several single nucleotide polymorphisms within the TCF7L2 gene have been associated with type 2 diabetes. Studies conducted by Ravindranath Duggirala and Michael Stern at The University of Texas Health Science Center at San Antonio were the first to identify strong linkage for type 2 diabetes at a region on Chromosome 10 in Mexican Americans This signal was later refined by Struan Grant and colleagues at DeCODE genetics and isolated to the TCF7L2 gene. The molecular and physiological mechanisms underlying the association of TCF7L2 with type 2 diabetes are under active investigation, but it is likely that TCF7L2 has important biological roles in multiple metabolic tissues, including the pancreas, liver and adipose tissue. TCF7L2 polymorphisms can increase susceptibility to type 2 diabetes by decreasing the production of glucagon-like peptide-1 (GLP-1).
## Gestational Diabetes (GDM)
TCF7L2 modulates pancreatic islet β-cell function strongly implicating its significant association with GDM risk. T alleles of rs7903146 and rs1799884 TCF7L2 polymorphisms increase susceptibility to GDM in the Chinese Han population.
## Cancer
TCF7L2 plays a role in colorectal cancer. A frameshift mutation of TCF7L2 provided evidence that TCF7L2 is implicated in colorectal cancer. The silencing of TCF7L2 in KM12 colorectal cancer cells provided evidence that TCF7L2 played a role in proliferation and metastasis of cancer cells in colorectal cancer.
Variants of the gene are most likely involved in many other cancer types. TCF7L2 is indirectly involved in prostate cancer through its role in activating the PI3K/Akt pathway, a pathway involved in prostate cancer.
## Schizophrenia
Single nucleotide polymorphisms (SNPs) in TCF7L2 gene have shown an increase in susceptibility to schizophrenia in Arab, European and Chinese Han populations. In the Chinese Han population, SNP rs12573128 in TCF7L2 is the variant that was associated with an increase in schizophrenia risk. This marker is used as a pre-diagnostic marker for schizophrenia.
## Multiple Sclerosis
TCF7L2 is downstream of the WNT/β-catenin pathways. The activation of the WNT/β-catenin pathways have been associated demyelination in multiple sclerosis. TCF7L2 is unregulated during early remyelination, leading scientists to believe that it is involved in remyelination. TCF7L2 could act in dependence or independent of the WNT/β-catenin pathways.
# Model organisms
Model organisms have been used in the study of TCF7L2 function. A conditional knockout mouse line called Tcf7l2tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping
Variations of the protein encoding gene are found in rats, zebra fish, drosophila, and budding yeast. Therefore, all of those organisms can be used as model organisms in the study of TCF7L2 function.
# Nomenclature
TCF7L2 is the symbol officially approved by the HUGO Gene Nomenclature Committee for the transcription factor 4 gene (TCF4). | TCF7L2
Transcription factor 7-like 2 (T-cell specific, HMG-box) also known as TCF7L2 or TCF4 is a protein acting as a transcription factor that in humans, is encoded by the TCF7L2 gene.[1][2] The TCF7L2 gene is located on chromosome 10q25.2-q25.3, contains 19 exons, and has autosomal dominant inheritance.[3][4] The TCF7L2 gene is polymorphic and pleiotropic.[5] As a member of the TCF family, TCF7L2 can form a bipartite transcription factor and influence several biological pathways, including the Wnt signalling pathway.[6] The single nucleotide polymorphism (SNP) within the TCF7L2 gene, rs7903146, is, to date, the most significant genetic marker[7] associated with Type 2 diabetes mellitus (T2DM) risk. SNPs in this gene are especially known to be linked to higher risk to develop type 2 diabetes,[6] gestational diabetes,[8] and multiple other diseases.[9][10][11]
# Function
TCF7L2 is a transcription factor influencing the transcription of several genes thereby exerting a large variety of functions within the cell. It is a member of the TCF family that can form a bipartite transcription factor (β-catenin/TCF) alongside β-catenin.[6] Bipartite transcription factors can have large effects on the Wnt signalling pathway.[6] Stimulation of the Wnt signaling pathway leads to the association of β-catenin with BCL9, translocation to the nucleus, and association with TCF7L2,[13] which in turn results in the activation of Wnt target genes. The activation of the Wnt target genes specifically represses proglucagon synthesis in enteroendocrine cells.[6][4] The repression of TCF7L2 using HMG-box repressor (HBP1) inhibits Wnt signalling.[6] Therefore, TCF7L2 is an effector in the Wnt signalling pathway. TCF7L2's role in glucose metabolism is expressed in many tissues such as gut, brain, liver, and skeletal muscle. However, TCF7L2 does not directly regulate glucose metabolism in β-cells, but regulates glucose metabolism in pancreatic and liver tissues.[14]
The TCF7L2 gene encoding the TCF7L2 transcription factor, exhibits multiple functions through its polymorphisms and thus, is known as a pleiotropic gene. Type 2 diabetes T2DM susceptibility is exhibited in carriers of TCF7L2 rs7903146C>T[15][5] and rs290481T>C[5] polymorphisms.[15][5] TCF7L2 rs290481T>C polymorphism, however, has shown no significant correlation to the susceptibility to gestational diabetes mellitus (GDM) in a Chinese Han population, whereas the T alleles of rs7903146[5] and rs1799884[8] increase susceptibility to GDM in the Chinese Han population.[5][8] The difference in effects of the different polymorphisms of the gene indicate that the gene is indeed pleiotropic.
# Structure
The TCF7L2 gene, encoding the TCF7L2 protein, is located on chromosome 10q25.2-q25.3. The gene contains 19 exons and has autosomal dominant inheritance.[3][4] Of the 19 exons, 5 are alternative.[4] The TCF7L2 gene contains 619 amino acids and its molecular mass is 67919 Da.[16] TCF7L2's secondary structure is a helix-turn-helix structure.[17]
# Tissue Distribution
TCF7L2 does not primarily operate in the β-cells in the pancreas.[18] It is also expressed in brain, liver, intestine, and fat cells.[18]
# Clinical significance
## Type 2 Diabetes
Several single nucleotide polymorphisms within the TCF7L2 gene have been associated with type 2 diabetes. Studies conducted by Ravindranath Duggirala and Michael Stern at The University of Texas Health Science Center at San Antonio were the first to identify strong linkage for type 2 diabetes at a region on Chromosome 10 in Mexican Americans [19] This signal was later refined by Struan Grant and colleagues at DeCODE genetics and isolated to the TCF7L2 gene.[20] The molecular and physiological mechanisms underlying the association of TCF7L2 with type 2 diabetes are under active investigation, but it is likely that TCF7L2 has important biological roles in multiple metabolic tissues, including the pancreas, liver and adipose tissue.[18][21] TCF7L2 polymorphisms can increase susceptibility to type 2 diabetes by decreasing the production of glucagon-like peptide-1 (GLP-1).[6]
## Gestational Diabetes (GDM)
TCF7L2 modulates pancreatic islet β-cell function strongly implicating its significant association with GDM risk.[8] T alleles of rs7903146[5] and rs1799884[8] TCF7L2 polymorphisms increase susceptibility to GDM in the Chinese Han population.[5][8]
## Cancer
TCF7L2 plays a role in colorectal cancer.[9] A frameshift mutation of TCF7L2 provided evidence that TCF7L2 is implicated in colorectal cancer.[22][23] The silencing of TCF7L2 in KM12 colorectal cancer cells provided evidence that TCF7L2 played a role in proliferation and metastasis of cancer cells in colorectal cancer.[9]
Variants of the gene are most likely involved in many other cancer types.[24] TCF7L2 is indirectly involved in prostate cancer through its role in activating the PI3K/Akt pathway, a pathway involved in prostate cancer.[25]
## Schizophrenia
Single nucleotide polymorphisms (SNPs) in TCF7L2 gene have shown an increase in susceptibility to schizophrenia in Arab, European and Chinese Han populations.[10] In the Chinese Han population, SNP rs12573128[10] in TCF7L2 is the variant that was associated with an increase in schizophrenia risk. This marker is used as a pre-diagnostic marker for schizophrenia.[10]
## Multiple Sclerosis
TCF7L2 is downstream of the WNT/β-catenin pathways. The activation of the WNT/β-catenin pathways have been associated demyelination in multiple sclerosis.[11] TCF7L2 is unregulated during early remyelination, leading scientists to believe that it is involved in remyelination.[11] TCF7L2 could act in dependence or independent of the WNT/β-catenin pathways.[11]
# Model organisms
Model organisms have been used in the study of TCF7L2 function. A conditional knockout mouse line called Tcf7l2tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[26] Male and female animals underwent a standardized phenotypic screen[27] to determine the effects of deletion.[28][29][30][31] Additional screens performed: - In-depth immunological phenotyping[32]
Variations of the protein encoding gene are found in rats, zebra fish, drosophila, and budding yeast.[33] Therefore, all of those organisms can be used as model organisms in the study of TCF7L2 function.
# Nomenclature
TCF7L2 is the symbol officially approved by the HUGO Gene Nomenclature Committee for the transcription factor 4 gene (TCF4). | https://www.wikidoc.org/index.php/TCF7L2 | |
9103c177d65760aed99ccd42d828881e8d43b008 | wikidoc | TCIRG1 | TCIRG1
V-type proton ATPase 116 kDa subunit a isoform 3 is an enzyme that in humans is encoded by the TCIRG1 gene.
# Function
Through alternate splicing, this gene encodes two protein isoforms with similarity to subunits of the vacuolar ATPase (V-ATPase) but the encoded proteins seem to have different functions. V-ATPase is a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, and receptor-mediated endocytosis. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain.
The two isoforms are:
- long isoform a, also named OC116
- short isoform b, also named TIRC7 (N-terminus truncated, lacks amino acid residues 1-216 of the long isoform)
TIRC7 is expressed in T lymphocytes and is essential for normal T cell activation. This variant uses a transcription start site that is within exon 5 of variant 1 followed by an intron as part of its 5' UTR.
# TIRC7
## Expression
TIRC7 is a membrane protein induced after immune activation on the cell surface of certain peripheral human T and B cells as well as monocytes and IL-10 expressing regulatory T cells. During immune activation, TIRC7 is co-localized with the T cell receptor and CTLA4 within the immune synapse of human T cells At the protein and mRNA level, its expression is induced in lymphocytes in synovial tissues obtained from patients with rheumatoid arthritis or during rejection of solid organ transplants and bone marrow transplantation as well as in brain tissues obtained from patients with multiple sclerosis.
## Function
Antibody targeting of TIRC7 reveals significant prevention of inflammation in variety of animal models e.g. rejection of transplanted kidney and heart allografts as well as progression of arthritis and EAE. These therapeutic effects were accompanied with significant decreases of Th1 specific cytokines e.g. IFN-gamma, TNF-alpha, IL-2 expression and transcription, induction of CTLA4 whereas IL-10 remained unchanged. The induction of TIRC7 in IL-10 secreting T regulatory cells and the prevention of colitis in the presence of TIRC7 positive T regulatory cells supports the inhibitory signals induced via TIRC7 pathway during immune activation. Further evidence for the inhibitory role of TIRC7 during the course of immune response is that prevention of colitis was achievable by a transfer of TIRC7 positive cells into CD45RO mice prior to induction of colitis. The negative immune regulatory role of TIRC7 is furthermore supported by the fact that TIRC7 knock out mice exhibits an increased T and B cell response in the presence of various stimuli in vitro and in vivo exhibiting. A significant induced memory cell subset and reduction of CTLA4 expression observed in TIRC7 knock out mice.
## Ligand
The recently identified cell surface ligand to TIRC7 is the non-polymorphic alpha 2 domain (HLA-DRα2) of HLA DR protein. Upon lymphocyte activation TIRC7 is upregulated to engage HLA-DRα2 and induce apoptotic signals in human CD4+ and CD8+ T-cells. The down-regulation of the immune response is achieved via activation of the intrinsic apoptotic pathway by caspase 9, inhibition of lymphocyte proliferation, SHP-1 recruitment, decrease in phosphorylation of STAT4, TCR-ζ chain and ZAP70 as well as inhibition of FasL expression. HLA-DRα2 and TIRC7 co-localize at the APC-T cell interaction site. In vivo, triggering the HLA-DR-TIRC7 pathway in lipopolysaccaride (LPS) activated lymphocytes using soluble HLA-DRα2 leads to inhibition of proinflammatory as well as inflammatory cytokines and induction of apoptosis. These results strongly support the regulatory role of TIRC7 signalling pathway in lymphocytes.
# Clinical significance
Mutations in this gene are associated with infantile malignant osteopetrosis. | TCIRG1
V-type proton ATPase 116 kDa subunit a isoform 3 is an enzyme that in humans is encoded by the TCIRG1 gene.[1][2][3]
# Function
Through alternate splicing, this gene encodes two protein isoforms with similarity to subunits of the vacuolar ATPase (V-ATPase) but the encoded proteins seem to have different functions. V-ATPase is a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, and receptor-mediated endocytosis. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain.
The two isoforms are:
- long isoform a, also named OC116
- short isoform b, also named TIRC7 (N-terminus truncated, lacks amino acid residues 1-216 of the long isoform)
TIRC7 is expressed in T lymphocytes and is essential for normal T cell activation. This variant uses a transcription start site that is within exon 5 of variant 1 followed by an intron as part of its 5' UTR.[4]
# TIRC7
## Expression
TIRC7 is a membrane protein induced after immune activation[2] on the cell surface of certain peripheral human T and B cells as well as monocytes and IL-10 expressing regulatory T cells. During immune activation, TIRC7 is co-localized with the T cell receptor and CTLA4 within the immune synapse of human T cells[5][6] At the protein and mRNA level, its expression is induced in lymphocytes in synovial tissues obtained from patients with rheumatoid arthritis[7][8] or during rejection of solid organ transplants[9][10][11] and bone marrow transplantation[12] as well as in brain tissues obtained from patients with multiple sclerosis.[13][14]
## Function
Antibody targeting of TIRC7 reveals significant prevention of inflammation in variety of animal models e.g. rejection of transplanted kidney and heart allografts[15][16] as well as progression of arthritis and EAE. These therapeutic effects were accompanied with significant decreases of Th1 specific cytokines e.g. IFN-gamma, TNF-alpha, IL-2 expression and transcription, induction of CTLA4 whereas IL-10 remained unchanged. The induction of TIRC7 in IL-10 secreting T regulatory cells and the prevention of colitis in the presence of TIRC7 positive T regulatory cells[17] supports the inhibitory signals induced via TIRC7 pathway during immune activation.[18] Further evidence for the inhibitory role of TIRC7 during the course of immune response is that prevention of colitis was achievable by a transfer of TIRC7 positive cells into CD45RO mice prior to induction of colitis. The negative immune regulatory role of TIRC7 is furthermore supported by the fact that TIRC7 knock out mice exhibits an increased T and B cell response in the presence of various stimuli in vitro and in vivo exhibiting. A significant induced memory cell subset and reduction of CTLA4 expression observed in TIRC7 knock out mice.[19]
## Ligand
The recently identified cell surface ligand to TIRC7 is the non-polymorphic alpha 2 domain (HLA-DRα2) of HLA DR protein.[20] Upon lymphocyte activation TIRC7 is upregulated to engage HLA-DRα2 and induce apoptotic signals in human CD4+ and CD8+ T-cells. The down-regulation of the immune response is achieved via activation of the intrinsic apoptotic pathway by caspase 9, inhibition of lymphocyte proliferation, SHP-1 recruitment, decrease in phosphorylation of STAT4, TCR-ζ chain and ZAP70 as well as inhibition of FasL expression. HLA-DRα2 and TIRC7 co-localize at the APC-T cell interaction site. In vivo, triggering the HLA-DR-TIRC7 pathway in lipopolysaccaride (LPS) activated lymphocytes using soluble HLA-DRα2 leads to inhibition of proinflammatory as well as inflammatory cytokines and induction of apoptosis. These results strongly support the regulatory role of TIRC7 signalling pathway in lymphocytes.
# Clinical significance
Mutations in this gene are associated with infantile malignant osteopetrosis.[3] | https://www.wikidoc.org/index.php/TCIRG1 | |
d808200bf76145fbbd7be7a3dadc4073e3387860 | wikidoc | TFAP2A | TFAP2A
Transcription factor AP-2 alpha (Activating enhancer binding Protein 2 alpha), also known as TFAP2A, is a protein that in humans is encoded by the TFAP2A gene.
# Function
The AP-2 alpha protein acts as a sequence-specific DNA-binding transcription factor recognizing and binding to the specific DNA sequence and recruiting transcription machinery. Its binding site is a GC-rich sequence that is present in the cis-regulatory regions of several viral and cellular genes. AP2-alpha is a 52-kD retinoic acid-inducible and developmentally regulated activator of transcription that binds to a consensus DNA-binding sequence GCCNNNGGC in the SV40 and metallothionein promoters.
AP-2 alpha is expressed in neural crest cell lineages with the highest levels of expression corresponding to early neural crest cells, suggesting that AP-2 alpha plays a role in their differentiation and development. Transcription factor AP-2 alpha is expressed in ectoderm and in neural-crest cells migrating from the cranial folds during closure of the neural tube in the mouse. Cranial neural crest cell provides patterning information for craniofacial morphogenesis and generate most of the skull bones and the cranial ganglia.
AP-2 alpha knockout mice die perinatally with cranio-abdominoschisis and severe dysmorphogenesis of the face, skull, sensory organs, and cranial ganglia. Homozygous knockout mice also have neural tube defects followed by craniofacial and body wall abnormalities. In vivo gene delivery of AP-2 alpha suppressed spontaneous intestinal polyps in the Apc(Min/+) mouse. AP-2 alpha also functions as a master regulator of multiple transcription factors in the mouse liver.
In melanocytic cells TFAP2A gene expression may be regulated by MITF.
# Clinical significance
Mutations in the TFAP2A gene cause Branchio-oculo-facial syndrome often with a midline cleft lip. In a family with branchio-oculo-facial syndrome (BOFS), a 3.2-Mb deletion at chromosome 6p24.3 was detected. Sequencing of candidate genes in that region in 4 additional unrelated BOFS patients revealed 4 different de novo missense mutations in the exons 4 and 5 of the TFAP2A gene.
A disruption of an AP-2 alpha binding site in an IRF6 enhancer is associated with cleft lip. Mutations in IRF6 gene cause Van der Woude syndrome (VWS) that is a rare mendelian clefting autossomal dominant disorder with lower lip pits in 85% of affected individuals. The remaining 15% of individuals with Van der Woude syndrome show only cleft lip and/or cleft palate (CL/P) and are clinically indistinguishable from the common non syndromic CL/P. NSCL/P occur in approximately 1/700 live births and is one of the most common form of congenital abnormalities. A previous association study between SNPs in and around IRF6 and NSCL/P have shown significant results in different populations and was independently replicated.
A search of NSCL/P cases for potential regulatory elements for IRF6 gene was made aligning genomic sequences to a 500 Kb region encompassing IRF6 from 17 vertebrate species. Human sequence as reference and searched for multispecies conserved sequences (MCSs). Regions contained in introns 5’ and 3’ flanking IRF6 were screened by direct sequencing for potential causative variants in 184 NSCL/P cases. The rare allele of the SNP rs642961 showed a significant association with cleft lip cases. Analysis of transcription factor binding site analysis showed that the risk allele disrupt a binding site for AP-2 alpha.
Mutations in the AP-2 alpha gene also cause branchio-oculo-facial syndrome, which has overlapping features with Van der Woude syndrome such as orofacial clefting and occasional lip pits what make rs642961 a good candidate for an etiological variant. These findings show that IRF6 and AP-2 alpha are in the same developmental pathway and identify a variant in a regulatory region that contributes substantially to a common complex disorder.
# Interactions
TFAP2A has been shown to interact with:
- APC
- CITED2
- DEK
- EP300
- Myc and
- P53. | TFAP2A
Transcription factor AP-2 alpha (Activating enhancer binding Protein 2 alpha), also known as TFAP2A, is a protein that in humans is encoded by the TFAP2A gene.[1]
# Function
The AP-2 alpha protein acts as a sequence-specific DNA-binding transcription factor recognizing and binding to the specific DNA sequence and recruiting transcription machinery. Its binding site is a GC-rich sequence that is present in the cis-regulatory regions of several viral and cellular genes.[2] AP2-alpha is a 52-kD retinoic acid-inducible and developmentally regulated activator of transcription that binds to a consensus DNA-binding sequence GCCNNNGGC in the SV40 and metallothionein promoters.[1]
AP-2 alpha is expressed in neural crest cell lineages with the highest levels of expression corresponding to early neural crest cells, suggesting that AP-2 alpha plays a role in their differentiation and development. Transcription factor AP-2 alpha is expressed in ectoderm and in neural-crest cells migrating from the cranial folds during closure of the neural tube in the mouse. Cranial neural crest cell provides patterning information for craniofacial morphogenesis and generate most of the skull bones and the cranial ganglia.[2][3][4][5]
AP-2 alpha knockout mice die perinatally with cranio-abdominoschisis and severe dysmorphogenesis of the face, skull, sensory organs, and cranial ganglia.[6] Homozygous knockout mice also have neural tube defects followed by craniofacial and body wall abnormalities.[7] In vivo gene delivery of AP-2 alpha suppressed spontaneous intestinal polyps in the Apc(Min/+) mouse.[8] AP-2 alpha also functions as a master regulator of multiple transcription factors in the mouse liver.[9]
In melanocytic cells TFAP2A gene expression may be regulated by MITF.[10]
# Clinical significance
Mutations in the TFAP2A gene cause Branchio-oculo-facial syndrome often with a midline cleft lip.[11] In a family with branchio-oculo-facial syndrome (BOFS),[12] a 3.2-Mb deletion at chromosome 6p24.3 was detected.[13] Sequencing of candidate genes in that region in 4 additional unrelated BOFS patients revealed 4 different de novo missense mutations in the exons 4 and 5 of the TFAP2A gene.
A disruption of an AP-2 alpha binding site in an IRF6 enhancer is associated with cleft lip.[14] Mutations in IRF6 gene cause Van der Woude syndrome (VWS)[15] that is a rare mendelian clefting autossomal dominant disorder with lower lip pits in 85% of affected individuals.[16] The remaining 15% of individuals with Van der Woude syndrome show only cleft lip and/or cleft palate (CL/P) and are clinically indistinguishable from the common non syndromic CL/P. NSCL/P occur in approximately 1/700 live births and is one of the most common form of congenital abnormalities. A previous association study between SNPs in and around IRF6 and NSCL/P have shown significant results in different populations[17] and was independently replicated.[18][19][20][21]
A search of NSCL/P cases for potential regulatory elements for IRF6 gene was made aligning genomic sequences to a 500 Kb region encompassing IRF6 from 17 vertebrate species. Human sequence as reference and searched for multispecies conserved sequences (MCSs). Regions contained in introns 5’ and 3’ flanking IRF6 were screened by direct sequencing for potential causative variants in 184 NSCL/P cases. The rare allele of the SNP rs642961 showed a significant association with cleft lip cases. Analysis of transcription factor binding site analysis showed that the risk allele disrupt a binding site for AP-2 alpha.[14]
Mutations in the AP-2 alpha gene also cause branchio-oculo-facial syndrome,[13] which has overlapping features with Van der Woude syndrome such as orofacial clefting and occasional lip pits what make rs642961 a good candidate for an etiological variant. These findings show that IRF6 and AP-2 alpha are in the same developmental pathway and identify a variant in a regulatory region that contributes substantially to a common complex disorder.
# Interactions
TFAP2A has been shown to interact with:
- APC[22]
- CITED2[23][24]
- DEK[25]
- EP300[23]
- Myc[26] and
- P53.[27] | https://www.wikidoc.org/index.php/TFAP2A | |
4f6e0099eff347be473f79206ffabdde507e8a77 | wikidoc | TFAP2B | TFAP2B
Transcription factor AP-2 beta also known as AP2-beta is a protein that in humans is encoded by the TFAP2B gene.
# Function
AP-2 beta is a member of the AP-2 family of transcription factors. AP-2 proteins form homo- or hetero-dimers with other AP-2 family members and bind specific DNA sequences. They are thought to stimulate cell proliferation and suppress terminal differentiation of specific cell types during embryonic development. Specific AP-2 family members differ in their expression patterns and binding affinity for different promoters. This protein functions as both a transcriptional activator and repressor.
# Clinical significance
Mutations in this gene result in autosomal dominant Char syndrome, suggesting that this gene functions in the differentiation of neural crest cell derivatives. | TFAP2B
Transcription factor AP-2 beta also known as AP2-beta is a protein that in humans is encoded by the TFAP2B gene.[1][2]
# Function
AP-2 beta is a member of the AP-2 family of transcription factors. AP-2 proteins form homo- or hetero-dimers with other AP-2 family members and bind specific DNA sequences. They are thought to stimulate cell proliferation and suppress terminal differentiation of specific cell types during embryonic development. Specific AP-2 family members differ in their expression patterns and binding affinity for different promoters. This protein functions as both a transcriptional activator and repressor.[3]
# Clinical significance
Mutations in this gene result in autosomal dominant Char syndrome, suggesting that this gene functions in the differentiation of neural crest cell derivatives.[3] | https://www.wikidoc.org/index.php/TFAP2B | |
08aca0b6df8ee1e3e9c2c7560283cf488dd3c284 | wikidoc | TIMM50 | TIMM50
Mitochondrial import inner membrane translocase subunit TIM50 is an enzyme that in humans is encoded by the TIMM50 gene. Tim50 is a subunit of the Tim23 translocase complex in the inner mitochondrial membrane. Mutations in TIMM50 can lead to epilepsy, severe intellectual disability, and 3-methylglutaconic aciduria. TIMM50 expression is increased in breast cancer cells and decreased in hypertrophic hearts.
# Structure
The TIMM50 gene is located on the q arm of chromosome 19 in position 13.2 and spans 13,373 base pairs. The gene produces a 39.6 kDa protein composed of 353 amino acids. This gene encodes a subunit of the TIM23 inner mitochondrial membrane translocase complex, which mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane.
# Function
The Tim50 protein functions as the receptor subunit that recognizes the mitochondrial targeting signal, or presequence, on protein cargo that is destined for the mitochondrial inner membrane and matrix. This gene in human cells results in the release of cytochrome c and apoptosis. This protein plays a role in maintaining the membrane permeability barrier. The intermembrane space domain of Tim50 induces the translocation pore of the TIM23 channel to close.
# Clinical significance
Missense mutations in TIMM50 often result in epilepsy or epileptic encephalopathy, severe intellectual disability, variable mitochondrial complex V deficiency, and 3-methylglutaconic aciduria, which is a key biomarker for mitochondrial membrane defects and mitochondrial dysfunction. Inheritance of TIMM50 is autosomal recessive. Expression of the TIMM50 gene is increased in breast cancer cells. In such cells, overexpression of the Tim50 protein is linked to lack of cellular apoptosis and increased rates of proliferation. Decreased TIMM50 expression in heart cells can lead to cardiac hypertrophy.
Two patients, male and female siblings born to consanguineous Bedouin parents were presented, displaying involuntary abnormal movements, failure to thrive, hypsarrhythmia, bilateral optic atrophy, 3-methylglutaconic aciduria, and slightly elevated plasma lactate levels. Both began walking independently at only 3 years and initially received favorably ACTH therapy until switching to a treatment of Valproate with either Sabril or Topamax, which resulted in seizures completely disappearing. Two more patients, male and female siblings born to first-cousin parents of Muslim origin were also presented, displaying myoclonic and tonic seizures, abnormal EEG, brain atrophy, delayed psychomotor development and 3-methylglutaconic aciduria. Treatment of Lamictal combined with Valproate was effective in controlling the seizures.
# Interactions
Within the TIM23 complex, the Tim50 subunit directly interacts with TIMM23. The TIM23 complex interacts with the TIMM44 component of the PAM complex and with DNAJC15. An isoform of Tim50 interacts with COIL and snRNPs.
# Reference
- ↑ Jump up to: 1.0 1.1 Yamamoto H, Esaki M, Kanamori T, Tamura Y, Nishikawa S, Endo T (November 2002). "TIM50 is a subunit of the Tim23 complex which links protein translocation across the outer and inner mitochondrial membranes". Cell. 111 (4): 519–28. doi:10.1016/S0092-8674(02)01053-X. PMID 12437925..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Jump up to: 2.0 2.1 2.2 2.3 2.4 "Entrez Gene: TIMM50 translocase of inner mitochondrial membrane 50 homolog (S. cerevisiae)".
- ↑ Jump up to: 3.0 3.1 3.2 Shahrour MA, Staretz-Chacham O, Dayan D, Stephen J, Weech A, Damseh N, et al. (May 2017). "Mitochondrial epileptic encephalopathy, 3-methylglutaconic aciduria and variable complex V deficiency associated with TIMM50 mutations". Clinical Genetics. 91 (5): 690–696. doi:10.1111/cge.12855. PMID 27573165.
- ↑ Jump up to: 4.0 4.1 Gao SP, Sun HF, Jiang HL, Li LD, Hu X, Xu XE, Jin W (January 2016). "Loss of TIM50 suppresses proliferation and induces apoptosis in breast cancer". Tumor Biology. 37 (1): 1279–87. doi:10.1007/s13277-015-3878-0. PMID 26289846.
- ↑ Jump up to: 5.0 5.1 Tang K, Zhao Y, Li H, Zhu M, Li W, Liu W, et al. (April 2017). "Translocase of Inner Membrane 50 Functions as a Novel Protective Regulator of Pathological Cardiac Hypertrophy". Journal of the American Heart Association. 6 (4): e004346. doi:10.1161/JAHA.116.004346. PMID 28432072.
- ↑ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, et al. (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
- ↑ "Mitochondrial import inner membrane translocase subunit TIM50". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
- ↑ "TIMM50 - Mitochondrial import inner membrane translocase subunit TIM50 precursor - Homo sapiens (Human) - TIMM50 gene & protein". www.uniprot.org. Retrieved 2018-07-25.
# Further reading
- Xu H, Somers ZB, Robinson ML, Hebert MD (July 2005). "Tim50a, a nuclear isoform of the mitochondrial Tim50, interacts with proteins involved in snRNP biogenesis". BMC Cell Biology. 6 (1): 29. doi:10.1186/1471-2121-6-29. PMC 1177934. PMID 16008839.
- Guo Y, Cheong N, Zhang Z, De Rose R, Deng Y, Farber SA, Fernandes-Alnemri T, Alnemri ES (June 2004). "Tim50, a component of the mitochondrial translocator, regulates mitochondrial integrity and cell death". The Journal of Biological Chemistry. 279 (23): 24813–25. doi:10.1074/jbc.M402049200. PMID 15044455.
- Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, et al. (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216.
- Yuryev A, Wennogle LP (February 2003). "Novel raf kinase protein-protein interactions found by an exhaustive yeast two-hybrid analysis". Genomics. 81 (2): 112–25. doi:10.1016/S0888-7543(02)00008-3. PMID 12620389.
This article incorporates text from the United States National Library of Medicine, which is in the public domain. | TIMM50
Mitochondrial import inner membrane translocase subunit TIM50 is an enzyme that in humans is encoded by the TIMM50 gene. Tim50 is a subunit of the Tim23 translocase complex in the inner mitochondrial membrane. [1][2] Mutations in TIMM50 can lead to epilepsy, severe intellectual disability, and 3-methylglutaconic aciduria.[3] TIMM50 expression is increased in breast cancer cells[4] and decreased in hypertrophic hearts.[5]
# Structure
The TIMM50 gene is located on the q arm of chromosome 19 in position 13.2 and spans 13,373 base pairs. [2] The gene produces a 39.6 kDa protein composed of 353 amino acids.[6][7] This gene encodes a subunit of the TIM23 inner mitochondrial membrane translocase complex, which mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane. [2]
# Function
The Tim50 protein functions as the receptor subunit that recognizes the mitochondrial targeting signal, or presequence, on protein cargo that is destined for the mitochondrial inner membrane and matrix. This gene in human cells results in the release of cytochrome c and apoptosis.[2] This protein plays a role in maintaining the membrane permeability barrier. The intermembrane space domain of Tim50 induces the translocation pore of the TIM23 channel to close. [1][2]
# Clinical significance
Missense mutations in TIMM50 often result in epilepsy or epileptic encephalopathy, severe intellectual disability, variable mitochondrial complex V deficiency, and 3-methylglutaconic aciduria, which is a key biomarker for mitochondrial membrane defects and mitochondrial dysfunction. Inheritance of TIMM50 is autosomal recessive. [3] Expression of the TIMM50 gene is increased in breast cancer cells. In such cells, overexpression of the Tim50 protein is linked to lack of cellular apoptosis and increased rates of proliferation.[4] Decreased TIMM50 expression in heart cells can lead to cardiac hypertrophy.[5]
Two patients, male and female siblings born to consanguineous Bedouin parents were presented, displaying involuntary abnormal movements, failure to thrive, hypsarrhythmia, bilateral optic atrophy, 3-methylglutaconic aciduria, and slightly elevated plasma lactate levels. Both began walking independently at only 3 years and initially received favorably ACTH therapy until switching to a treatment of Valproate with either Sabril or Topamax, which resulted in seizures completely disappearing. Two more patients, male and female siblings born to first-cousin parents of Muslim origin were also presented, displaying myoclonic and tonic seizures, abnormal EEG, brain atrophy, delayed psychomotor development and 3-methylglutaconic aciduria. Treatment of Lamictal combined with Valproate was effective in controlling the seizures.[3]
# Interactions
Within the TIM23 complex, the Tim50 subunit directly interacts with TIMM23. The TIM23 complex interacts with the TIMM44 component of the PAM complex and with DNAJC15. An isoform of Tim50 interacts with COIL and snRNPs.[8]
# Reference
- ↑ Jump up to: 1.0 1.1 Yamamoto H, Esaki M, Kanamori T, Tamura Y, Nishikawa S, Endo T (November 2002). "TIM50 is a subunit of the Tim23 complex which links protein translocation across the outer and inner mitochondrial membranes". Cell. 111 (4): 519–28. doi:10.1016/S0092-8674(02)01053-X. PMID 12437925..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Jump up to: 2.0 2.1 2.2 2.3 2.4 "Entrez Gene: TIMM50 translocase of inner mitochondrial membrane 50 homolog (S. cerevisiae)".
- ↑ Jump up to: 3.0 3.1 3.2 Shahrour MA, Staretz-Chacham O, Dayan D, Stephen J, Weech A, Damseh N, et al. (May 2017). "Mitochondrial epileptic encephalopathy, 3-methylglutaconic aciduria and variable complex V deficiency associated with TIMM50 mutations". Clinical Genetics. 91 (5): 690–696. doi:10.1111/cge.12855. PMID 27573165.
- ↑ Jump up to: 4.0 4.1 Gao SP, Sun HF, Jiang HL, Li LD, Hu X, Xu XE, Jin W (January 2016). "Loss of TIM50 suppresses proliferation and induces apoptosis in breast cancer". Tumor Biology. 37 (1): 1279–87. doi:10.1007/s13277-015-3878-0. PMID 26289846.
- ↑ Jump up to: 5.0 5.1 Tang K, Zhao Y, Li H, Zhu M, Li W, Liu W, et al. (April 2017). "Translocase of Inner Membrane 50 Functions as a Novel Protective Regulator of Pathological Cardiac Hypertrophy". Journal of the American Heart Association. 6 (4): e004346. doi:10.1161/JAHA.116.004346. PMID 28432072.
- ↑ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, et al. (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
- ↑ "Mitochondrial import inner membrane translocase subunit TIM50". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
- ↑ "TIMM50 - Mitochondrial import inner membrane translocase subunit TIM50 precursor - Homo sapiens (Human) - TIMM50 gene & protein". www.uniprot.org. Retrieved 2018-07-25.
# Further reading
- Xu H, Somers ZB, Robinson ML, Hebert MD (July 2005). "Tim50a, a nuclear isoform of the mitochondrial Tim50, interacts with proteins involved in snRNP biogenesis". BMC Cell Biology. 6 (1): 29. doi:10.1186/1471-2121-6-29. PMC 1177934. PMID 16008839.
- Guo Y, Cheong N, Zhang Z, De Rose R, Deng Y, Farber SA, Fernandes-Alnemri T, Alnemri ES (June 2004). "Tim50, a component of the mitochondrial translocator, regulates mitochondrial integrity and cell death". The Journal of Biological Chemistry. 279 (23): 24813–25. doi:10.1074/jbc.M402049200. PMID 15044455.
- Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, et al. (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216.
- Yuryev A, Wennogle LP (February 2003). "Novel raf kinase protein-protein interactions found by an exhaustive yeast two-hybrid analysis". Genomics. 81 (2): 112–25. doi:10.1016/S0888-7543(02)00008-3. PMID 12620389.
This article incorporates text from the United States National Library of Medicine, which is in the public domain. | https://www.wikidoc.org/index.php/TIMM50 | |
e56da21a974c28cc0d5005afd55b35eaa03023e2 | wikidoc | TIMM8A | TIMM8A
Mitochondrial import inner membrane translocase subunit Tim8 A, also known as Deafness-dystonia peptide or protein is an enzyme that in humans is encoded by the TIMM8A gene. This translocase has similarity to yeast mitochondrial proteins that are involved in the import of metabolite transporters from the cytoplasm into the mitochondrial inner membrane. The gene is mutated in Deafness-dystonia syndrome (or Mohr-Tranebjaerg syndrome; MTS/DFN-1) and it is postulated that MTS/DFN-1 is a mitochondrial disease caused by a defective mitochondrial protein import system.
# Structure
The TIMM8A gene is located on q arm of chromosome X in position 22.1 and spans 3,313 base pairs. The gene produces an 11 kDa protein composed of 97 amino acids. The structure shows resemblance to yeast translocase of the inner membrane (TIM) proteins with two conserved paired cysteine residue motifs. The cysteine residues organize zinc ions for stability and control other interactions with proteins.
# Function
The human TIMM8A gene codes for a translocase involved in the import and insertion of hydrophobic membrane proteins from the cytoplasm into the mitochondrial inner membrane. It is also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. It acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space. The TIMM8-TIMM13 complex mediates the import of proteins such as TIMM23, SLC25A12/ARALAR1 and SLC25A13/ARALAR2, while the predominant TIMM9-TIMM10 70 kDa complex mediates the import of much more proteins. TIMM8A has been implicated as a required element in normal neurologic development.
# Clinical significance
Mutation of TIMM8A is associated with Mohr-Tranebjaerg syndrome/Deafness Dystonia Syndrome (MTS/DDS), a mitochondrial disease postulated to be associated with a defective mitochondrial protein import system.Mohr-Tranebjaerg syndrome is a recessive, X-linked neurodegenerative syndrome characterized by early-onset deafness followed by progressive dystonia in adulthood, progressive sensorineural hearing loss, mental retardation, dysphagia, paranoia, and cortical blindness. It is known to be caused by a truncation or deletion of the 11 kDa protein product of TIMM8A. Defects in this gene also cause Jensen syndrome, an X-linked disease with opticoacoustic nerve atrophy and muscle weakness.
A 39-year-old Japanese male patient with a nonsense mutation of the CGA codon 80 of exon 2 by TGA in the TIMM8A gene was diagnosed with Deafness-dystonia syndrome. Signs and symptoms included sensorineural deafness, dystonia, blepharospasm, brisk deep tendon reflexes and personality changes. However, there were no visual or sensory disturbances. The mother was found to be a heterozygous carrier for the mutation. Another patient, an 11-year-old Dutch child with a de novo missense mutation (C66W; c.233C > G) in the TIMM8A gene, was diagnosed with sensorineural hearing
impairment associated with Deafness-dystonia syndrome. Signs and symptoms included hyperreflexia, dyspraxia, synkinesis, atrophy, and progressive dystonia. A third patient, a 30-year-old male with Deafness-dystonia syndrome, was found to have a novel 108delG mutation in the TIMM8A gene. Signs and symptoms were generalized dystonia, scoliosis, blepharospasm, and involuntary movements of the head and neck. There are many more cases of mutations in the TIMM8A gene with varying symptoms, commonly including dystonia, mental deficiency, sensorineural hearing loss, optic atrophy, and others.
# Interactions
TIMM8A has been shown to interact with Signal transducing adaptor molecule and TIMM13. Three copies of TIMM8A and three copies of TIMM13 assemble to form a 70 kDa TIMM8-TIMM13 Complex with heterohexamer structure in the intermembrane space. The TIMM8-TIMM13 Complex associates with the TIM22 complex whose core is composed of TIMM22 to import and assemble inner membrane proteins. | TIMM8A
Mitochondrial import inner membrane translocase subunit Tim8 A, also known as Deafness-dystonia peptide or protein is an enzyme that in humans is encoded by the TIMM8A gene.[1][2][3] This translocase has similarity to yeast mitochondrial proteins that are involved in the import of metabolite transporters from the cytoplasm into the mitochondrial inner membrane. The gene is mutated in Deafness-dystonia syndrome (or Mohr-Tranebjaerg syndrome; MTS/DFN-1) and it is postulated that MTS/DFN-1 is a mitochondrial disease caused by a defective mitochondrial protein import system.[3]
# Structure
The TIMM8A gene is located on q arm of chromosome X in position 22.1 and spans 3,313 base pairs.[4] The gene produces an 11 kDa protein composed of 97 amino acids.[5][6] The structure shows resemblance to yeast translocase of the inner membrane (TIM) proteins with two conserved paired cysteine residue motifs.[7] The cysteine residues organize zinc ions for stability and control other interactions with proteins.[7]
# Function
The human TIMM8A gene codes for a translocase involved in the import and insertion of hydrophobic membrane proteins from the cytoplasm into the mitochondrial inner membrane.[4] It is also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. It acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space. The TIMM8-TIMM13 complex mediates the import of proteins such as TIMM23, SLC25A12/ARALAR1 and SLC25A13/ARALAR2, while the predominant TIMM9-TIMM10 70 kDa complex mediates the import of much more proteins. TIMM8A has been implicated as a required element in normal neurologic development.[8]
# Clinical significance
Mutation of TIMM8A is associated with Mohr-Tranebjaerg syndrome/Deafness Dystonia Syndrome (MTS/DDS), a mitochondrial disease postulated to be associated with a defective mitochondrial protein import system.[3]Mohr-Tranebjaerg syndrome is a recessive, X-linked neurodegenerative syndrome characterized by early-onset deafness followed by progressive dystonia in adulthood, progressive sensorineural hearing loss, mental retardation, dysphagia, paranoia, and cortical blindness.[9][10] It is known to be caused by a truncation or deletion of the 11 kDa protein product of TIMM8A.[11] Defects in this gene also cause Jensen syndrome, an X-linked disease with opticoacoustic nerve atrophy and muscle weakness.[4]
A 39-year-old Japanese male patient with a nonsense mutation of the CGA codon 80 of exon 2 by TGA in the TIMM8A gene was diagnosed with Deafness-dystonia syndrome. Signs and symptoms included sensorineural deafness, dystonia, blepharospasm, brisk deep tendon reflexes and personality changes. However, there were no visual or sensory disturbances. The mother was found to be a heterozygous carrier for the mutation.[9] Another patient, an 11-year-old Dutch child with a de novo missense mutation (C66W; c.233C > G) in the TIMM8A gene, was diagnosed with sensorineural hearing
impairment associated with Deafness-dystonia syndrome. Signs and symptoms included hyperreflexia, dyspraxia, synkinesis, atrophy, and progressive dystonia.[12] A third patient, a 30-year-old male with Deafness-dystonia syndrome, was found to have a novel 108delG mutation in the TIMM8A gene. Signs and symptoms were generalized dystonia, scoliosis, blepharospasm, and involuntary movements of the head and neck.[13] There are many more cases of mutations in the TIMM8A gene with varying symptoms, commonly including dystonia, mental deficiency, sensorineural hearing loss, optic atrophy, and others.[14][15][16][17][18]
# Interactions
TIMM8A has been shown to interact with Signal transducing adaptor molecule[7] and TIMM13.[19][20] Three copies of TIMM8A and three copies of TIMM13 assemble to form a 70 kDa TIMM8-TIMM13 Complex with heterohexamer structure in the intermembrane space.[20][8] The TIMM8-TIMM13 Complex associates with the TIM22 complex whose core is composed of TIMM22 to import and assemble inner membrane proteins.[8] | https://www.wikidoc.org/index.php/TIMM8A | |
9194bff40b6a0420b3e6e877c87d3c99cea25a93 | wikidoc | TM6SF2 | TM6SF2
TM6SF2 is the Transmembrane 6 superfamily 2 human gene which codes for a protein by the same name. This gene is otherwise called KIAA1926. Its exact function is currently unknown.
# Location
TM6SF2 is located on chromosome 19 precisely at locus 19p13.3-p12. It is flanked by SUGP1 (a SURP and G-Patch Domain-Containing protein thought to play a role in pre-mRNA splicing ) and HAPLN4 (a hyaluronan and proteoglycan link protein 4 that binds to hyaluronic acid and may be involved in formation of the extracellular matrix ) genes upstream and downstream respectively.
# Evolutionary aspects
## Orthologs
TM6SF2 is a moderately conserved gene. There exist orthologs in several phyla as far diverged as invertebrates. 82 organisms have been identified as having orthologs of this gene. The most distant orthologs of TM6SF2 are in zebra fish (Danio rerio) and the deer tick (Ixodes scapularis). Below is a summary table of some of the gene orthologs obtained from the NCBI database.
## Paralogs
TM6SF1 has been identified as a paralog of TM6SF2 in humans about which little is known.
## Homologous domains
The domain of unknown function DUF2781 is highly conserved across homologs. DUF2781 belongs to the pfam10914 family which comprises uncharacterized eukaryotic proteins, some of which are membrane proteins
# mRNA
The RNA product is 1483 base pairs long and is spliced alternatively to yield seven different isoforms (alternative mRNAs a - f with form a being the most abundant) with varying combinations of the 10 identified exons. The microRNA miR-1343 binds to a 3’ UTR site called 7mer-m8 (as predicted by TargetScan).
## Folding patterns
The 5' and 3' UTR regions of the mRNA show some stem loop formation for stability. Much of this chemistry appears to be taking place in the 5' region which has three stem loops compared to the 3' region with only one.
## Exons and introns
There are ten different exons and the ones expressed depend on how alternative splicing proceeds. There are four alternative polyadenylation sites present.
# Promoter region
The promoter for this gene is upstream and spans bases 19383923 to 19384700 (778 bp long) on the minus strand of chromosome 19. There exist several transcription factors capable of binding to this promoter region including cAMP responsive element binding protein, SMAD3, KLF3, EGR1, SOX/SRY, PAX2/PAX5 and two SNP regions have been identified as well. The transcription factors predicted to bind the TM6SF2 promoter suggest this protein functions in growth and tumor regulation as well as sex determination to a lesser extent.
# Protein
The TM6SF2 protein contains 377 amino acids and is 42,554 Da large with an isoelectric point of about 7.7.
## Domains and motifs
There is a domain of unknown function, DUF2781 ( pfam10914 family) spanning amino acids 218 to 359 in the C-terminus of the protein.
There are nine transmembrane regions in this protein. The first one contains the signal peptide which is eventually cleaved following protein localization to the ER. A terminal KHHQ sequence is an endoplasmic reticulum retention signal.
## Secondary structure
Several alpha helices and beta strands are formed by the mature protein with as many as thirteen helices (including transmembrane helices) and fifteen beta sheets predicted.
## 3° and 4° structure
The protein side groups in this protein do not necessarily interact in a manner to form tertiary and quaternary structures. The cysteines present are not predicted to form stable disulfide bonds.
## Post-translational modifications
Two main post-translational modifications occur; phosphorylation at tyrosine, serine and tryptophan sites and two low probability sumoylation sites.
## Expression patterns
In humans, TM6SF2 expression has been documented in the adult stage only specifically in the intestine and liver in moderate amounts as well as embryonic tissue and ovary at low levels. Other sources indicate expression in brain, lung, testis, stomach, heart, colon, kidney and adipose tissue.
Protein subcellular localization studies with confocal microscopy demonstrated that TM6SF2 is localized in the endoplasmic reticulum and the ER-Golgi intermediate compartment of human liver cells.
## Protein interactions
No known protein-protein interactions have been established thus far.
# Clinical significance
In a study that used pre-made kits to predict cardiac allograft rejection using peripheral blood only, graft rejection was associated with decreased levels of TM6SF2 expression, alongside other genes.
A variant TM6SF2 gene causes susceptibility to nonalcoholic fatty liver disease due to impaired very low density lipoprotein (VLDL) production14.
TM6SF2 inhibition was associated with reduced secretion of TG-rich lipoproteins (TRLs) and increased cellular TG concentration and lipid droplet content, whereas TM6SF2 overexpression reduced liver cell steatosis. TM6SF2 is a regulator of liver fat metabolism with opposing effects on the secretion of TRLs and hepatic lipid droplet content. | TM6SF2
TM6SF2 is the Transmembrane 6 superfamily 2 human gene which codes for a protein by the same name. This gene is otherwise called KIAA1926.[1] Its exact function is currently unknown.
# Location
TM6SF2 is located on chromosome 19 precisely at locus 19p13.3-p12. It is flanked by SUGP1 (a SURP and G-Patch Domain-Containing protein thought to play a role in pre-mRNA splicing [1]) and HAPLN4 (a hyaluronan and proteoglycan link protein 4 that binds to hyaluronic acid and may be involved in formation of the extracellular matrix [1]) genes upstream and downstream respectively.[2]
# Evolutionary aspects
## Orthologs
TM6SF2 is a moderately conserved gene. There exist orthologs in several phyla as far diverged as invertebrates. 82 organisms have been identified as having orthologs of this gene. The most distant orthologs of TM6SF2 are in zebra fish (Danio rerio) and the deer tick (Ixodes scapularis).[2] Below is a summary table of some of the gene orthologs obtained from the NCBI database.
## Paralogs
TM6SF1 has been identified as a paralog of TM6SF2 in humans [2] about which little is known.
## Homologous domains
The domain of unknown function DUF2781 is highly conserved across homologs. DUF2781 belongs to the pfam10914 family which comprises uncharacterized eukaryotic proteins, some of which are membrane proteins [2]
# mRNA
The RNA product is 1483 base pairs long and is spliced alternatively to yield seven different isoforms (alternative mRNAs a - f with form a being the most abundant) with varying combinations of the 10 identified exons.[3] The microRNA miR-1343 binds to a 3’ UTR site called 7mer-m8 (as predicted by TargetScan[4]).
## Folding patterns
The 5' and 3' UTR regions of the mRNA show some stem loop formation for stability. Much of this chemistry appears to be taking place in the 5' region which has three stem loops compared to the 3' region with only one.[5]
## Exons and introns
There are ten different exons and the ones expressed depend on how alternative splicing proceeds. There are four alternative polyadenylation sites present.[3]
# Promoter region
The promoter for this gene is upstream and spans bases 19383923 to 19384700 (778 bp long) on the minus strand of chromosome 19. There exist several transcription factors capable of binding to this promoter region including cAMP responsive element binding protein, SMAD3, KLF3, EGR1, SOX/SRY, PAX2/PAX5[6] and two SNP regions have been identified as well.[7] The transcription factors predicted to bind the TM6SF2 promoter suggest this protein functions in growth and tumor regulation as well as sex determination to a lesser extent.
# Protein
The TM6SF2 protein contains 377 amino acids and is 42,554 Da large with an isoelectric point of about 7.7.[8]
## Domains and motifs
There is a domain of unknown function, DUF2781 ( pfam10914 family) spanning amino acids 218 to 359 in the C-terminus of the protein.[2]
There are nine transmembrane regions in this protein. The first one contains the signal peptide which is eventually cleaved following protein localization to the ER. A terminal KHHQ sequence is an endoplasmic reticulum retention signal.[9]
## Secondary structure
Several alpha helices and beta strands are formed by the mature protein with as many as thirteen helices (including transmembrane helices) and fifteen beta sheets predicted.[10]
## 3° and 4° structure
The protein side groups in this protein do not necessarily interact in a manner to form tertiary and quaternary structures. The cysteines present are not predicted to form stable disulfide bonds.[11]
## Post-translational modifications
Two main post-translational modifications occur; phosphorylation at tyrosine, serine and tryptophan sites and two low probability sumoylation sites.[12]
## Expression patterns
In humans, TM6SF2 expression has been documented in the adult stage only specifically in the intestine and liver in moderate amounts as well as embryonic tissue and ovary at low levels. Other sources indicate expression in brain, lung, testis, stomach, heart, colon, kidney and adipose tissue.[13]
Protein subcellular localization studies with confocal microscopy demonstrated that TM6SF2 is localized in the endoplasmic reticulum and the ER-Golgi intermediate compartment of human liver cells.[14]
## Protein interactions
No known protein-protein interactions have been established thus far.[15][16][17]
# Clinical significance
In a study that used pre-made kits to predict cardiac allograft rejection using peripheral blood only, graft rejection was associated with decreased levels of TM6SF2 expression, alongside other genes.[18]
A variant TM6SF2 gene causes susceptibility to nonalcoholic fatty liver disease due to impaired very low density lipoprotein (VLDL) production14.[19]
TM6SF2 inhibition was associated with reduced secretion of TG-rich lipoproteins (TRLs) and increased cellular TG concentration and lipid droplet content, whereas TM6SF2 overexpression reduced liver cell steatosis. TM6SF2 is a regulator of liver fat metabolism with opposing effects on the secretion of TRLs and hepatic lipid droplet content.[14] | https://www.wikidoc.org/index.php/TM6SF2 | |
4453b0b653148e3de69507f00fb9c95949c58467 | wikidoc | TMEM18 | TMEM18
Transmembrane protein 18 also known as TMEM18 is a protein which in humans is encoded by the TMEM18 gene.
# Function
TMEM18 seems to affect energy levels through insulin and glucagon signaling, and in flies, its downregulation induces a metabolic state resembling type-II diabetes
Overexpression of the TMEM18 protein increases the migration capacity of neural stem cells while inactivation of TMEM18 results in almost complete loss of migration activity.
The TMEM18 gene is ubiquitously expressed in both mammalian and fly tissues, which suggests a basic cellular function. In the mouse brain, it is found in the majority of all cells, but is more abundant in neurons than other cell types.
# Clinical significance
Genetic variants in the proximity of the TMEM18 gene are associated with obesity, insulin levels, and blood sugar levels
# Evolutionary history
The TMEM18 gene has a long evolutionary history as it is present in both plants and animals. The TMEM18 protein's amino acid sequence is well conserved, which suggests that it has retained its function since the divergence of human and plants. The gene seems to have been lost in two separate lineages, but is not found duplicated in any analyzed genomes. Hence, it is not essential for eukaryotic organisms, but there appears to be selection against multiple copies of the TMEM18 gene. | TMEM18
Transmembrane protein 18 also known as TMEM18 is a protein which in humans is encoded by the TMEM18 gene.[1]
# Function
TMEM18 seems to affect energy levels through insulin and glucagon signaling, and in flies, its downregulation induces a metabolic state resembling type-II diabetes[2]
Overexpression of the TMEM18 protein increases the migration capacity of neural stem cells while inactivation of TMEM18 results in almost complete loss of migration activity.[3]
The TMEM18 gene is ubiquitously expressed in both mammalian and fly tissues,[2] which suggests a basic cellular function. In the mouse brain, it is found in the majority of all cells, but is more abundant in neurons than other cell types.[4]
# Clinical significance
Genetic variants in the proximity of the TMEM18 gene are associated with obesity,[4][5][6][7][8] insulin levels, and blood sugar levels [2]
# Evolutionary history
The TMEM18 gene has a long evolutionary history as it is present in both plants and animals.[2][4] The TMEM18 protein's amino acid sequence is well conserved, which suggests that it has retained its function since the divergence of human and plants. The gene seems to have been lost in two separate lineages, but is not found duplicated in any analyzed genomes. Hence, it is not essential for eukaryotic organisms, but there appears to be selection against multiple copies of the TMEM18 gene.[2] | https://www.wikidoc.org/index.php/TMEM18 | |
fd3fc7e69063d59f9d9f1c13d799c576def8a4c9 | wikidoc | TMEM44 | TMEM44
TMEM44 (Transmembrane protein 44) is a protein that in humans is encoded by the TMEM44 gene. DKFZp686O18124 is a synonym of TMEM44.
# Gene
TMEM44 gene has 14 transcipts (splice variants). The whole span of the gene is 46,016 base pairs long, while the mRNA sequence of TMEM44 is 1,483 base pairs long, with 13 exons. Exon 1 and 2 partial are part of 5'-UTR, and the partial exon 2 is only highly conserved in primates.
## Regulation
There are 5 experimentally verified promoters, and 4 predicted ones. Promoter GXP_232172, which is promoter set 5 is the longest with 1,276 base pairs and a total of 11 coding transcripts.
## Expression
There is an overall low level expression of TMEM44 gene throughout the body parts and throughout the developmental stages of humans. Some parts where TMEM44 expression is detected are in bone, brain, eye, ovary, pancreas and uterus. Some expression was also detected under certain health conditions including gastrointestinal tumor, glioma, ovarian tumor, pancreatic tumor, muscle tissue tumor and uterine tumor.
# Locus
TMEM44 gene is located near the end of the long arm of chromosome 3 (3q29) in humans (Homo sapiens).
# Protein
TMEM44 is 428 amino acids in length. The molecular weight of the protein is 47.1kDa, and its formula is C2086H3315N585O611S22, with a total of 6,619 atoms. The theoretical isoelectric point (pI) of TMEM44 is 8.12. The instability index (II) of TMEM44 is 47.96, which classifies the protein as unstable. There are 12 isoforms of TMEM44, with isofrom c being the longest. The function of TMEM44 is currently unknown.
## Subcellular Localization
The C-terminus of TMEM44 is found in the cytoplasm, and the protein is predicted to be integrated within the membrane of the endoplasmic reticulum.
## Secondary Structure
TMEM44 has 41.12% of alpha helix, 15.65% of extended strand and 43.22% of random coil.
### Transmembrane Region Allocation
There are seven predicted transmembrane domains in TMEM44 protein.
## Interacting Proteins
GSK3B (Glycogen synthase kinase 3 beta), KAT6B (Histone acetyltransferase KAT6B/Histone acetyltransferase MYST4), TMEM31 (Transmembrane protein 31), SPAG9 (sperm associated antigen 9) and TNKS (tankyrase-1) are predicted to interact with TMEM44.
## Post-Translational Modification
TMEM44 undergoes threonine, tyrosine and serine phosphorylations. Many serine phosphorylation takes place near the C-terminus, causing it to be negatively charged.
The Glycine (G) found nearest from the C-terminus is predicted to have glycosylphosphatidylinositol (GPI) attached, which anchors the protein to the cellular plasma membrane.
The first 45 amino acids serve as a signal peptide cleavage site .
## Conservation
### Orthologs
Orthologs with the TMEM44 protein include amphibians, birds, fish, and mammals. The closest ortholog from human with TMEM44 is common chimpanzee (Pan troglodytes) with 98% identity, and the most distantly related ortholog is common carp (Cyprinus carpio) with 27% identity.
12 selected orthologs of TMEM44 are shown below.
TMEM44 is generally fast evolving, with about 0.310 changes of amino acids per 100 over a million year.
### Paralogs
Predicted paralogous proteins of TMEM44 are C9IZ85, F8WCY1, F8WE47, H7C3X7, J3KQW3, Q6PL43, and Q96I73. | TMEM44
TMEM44 (Transmembrane protein 44) is a protein that in humans is encoded by the TMEM44 gene[1]. DKFZp686O18124 is a synonym of TMEM44.
# Gene
TMEM44 gene has 14 transcipts (splice variants). The whole span of the gene is 46,016 base pairs long, while the mRNA sequence of TMEM44 is 1,483 base pairs long, with 13 exons. Exon 1 and 2 partial are part of 5'-UTR, and the partial exon 2 is only highly conserved in primates[2].
## Regulation
There are 5 experimentally verified promoters, and 4 predicted ones. Promoter GXP_232172, which is promoter set 5 is the longest with 1,276 base pairs and a total of 11 coding transcripts[3].
## Expression
There is an overall low level expression of TMEM44 gene throughout the body parts and throughout the developmental stages of humans. Some parts where TMEM44 expression is detected are in bone, brain, eye, ovary, pancreas and uterus. Some expression was also detected under certain health conditions including gastrointestinal tumor, glioma, ovarian tumor, pancreatic tumor, muscle tissue tumor and uterine tumor[4].
# Locus
TMEM44 gene is located near the end of the long arm of chromosome 3 (3q29) in humans (Homo sapiens)[5].
# Protein
TMEM44 is 428 amino acids in length. The molecular weight of the protein is 47.1kDa, and its formula is C2086H3315N585O611S22, with a total of 6,619 atoms[6]. The theoretical isoelectric point (pI) of TMEM44 is 8.12[7]. The instability index (II) of TMEM44 is 47.96, which classifies the protein as unstable. There are 12 isoforms of TMEM44, with isofrom c being the longest[5]. The function of TMEM44 is currently unknown.
## Subcellular Localization
The C-terminus of TMEM44 is found in the cytoplasm, and the protein is predicted to be integrated within the membrane of the endoplasmic reticulum[8].
## Secondary Structure
TMEM44 has 41.12% of alpha helix, 15.65% of extended strand and 43.22% of random coil[9].
### Transmembrane Region Allocation
There are seven predicted transmembrane domains in TMEM44 protein.
## Interacting Proteins
GSK3B (Glycogen synthase kinase 3 beta), KAT6B (Histone acetyltransferase KAT6B/Histone acetyltransferase MYST4), TMEM31 (Transmembrane protein 31), SPAG9 (sperm associated antigen 9) and TNKS (tankyrase-1) are predicted to interact with TMEM44[10][11][12].
## Post-Translational Modification
TMEM44 undergoes threonine, tyrosine and serine phosphorylations[13]. Many serine phosphorylation takes place near the C-terminus, causing it to be negatively charged.
The Glycine (G) found nearest from the C-terminus is predicted to have glycosylphosphatidylinositol (GPI) attached, which anchors the protein to the cellular plasma membrane[14].
The first 45 amino acids serve as a signal peptide cleavage site [15].
## Conservation
### Orthologs
Orthologs with the TMEM44 protein include amphibians, birds, fish, and mammals. The closest ortholog from human with TMEM44 is common chimpanzee (Pan troglodytes) with 98% identity, and the most distantly related ortholog is common carp (Cyprinus carpio) with 27% identity[16].
12 selected orthologs of TMEM44 are shown below.
TMEM44 is generally fast evolving, with about 0.310 changes of amino acids per 100 over a million year.
### Paralogs
Predicted paralogous proteins of TMEM44 are C9IZ85, F8WCY1, F8WE47, H7C3X7, J3KQW3, Q6PL43, and Q96I73[18]. | https://www.wikidoc.org/index.php/TMEM44 | |
eeccbc472a8afae69f071d33d62ef1ecf7cc6d72 | wikidoc | TMEM67 | TMEM67
Meckelin is a protein that in humans is encoded by the TMEM67 gene.
# Function
The protein encoded by this gene localizes to the primary cilium and to the plasma membrane. The gene functions in centriole migration to the apical membrane and formation of the primary cilium. Multiple transcript variants encoding different isoforms have been found for this gene.
# Clinical significance
Defects in this gene are a cause of Meckel syndrome type 3 (MKS3), nephronophthisis and Joubert syndrome type 6 (JBTS6). | TMEM67
Meckelin is a protein that in humans is encoded by the TMEM67 gene.[1][2][3]
# Function
The protein encoded by this gene localizes to the primary cilium and to the plasma membrane. The gene functions in centriole migration to the apical membrane and formation of the primary cilium. Multiple transcript variants encoding different isoforms have been found for this gene.[3]
# Clinical significance
Defects in this gene are a cause of Meckel syndrome type 3 (MKS3),[2] nephronophthisis[4][5] and Joubert syndrome type 6 (JBTS6).[6] | https://www.wikidoc.org/index.php/TMEM67 | |
ec3afa27c06a8b698dcc06238134a7394e03f6f9 | wikidoc | TMEM69 | TMEM69
TMEM69, also known as Transmembrane protein 69, is a protein that in humans is encoded by the TMEM69 gene. A notable feature of the protein encoded by TMEM69 is the presence of five transmembrane segments.
# Background Information
# Gene
The TMEM69 gene, located on chromosome 1p34.1, covers 7.24 kb. It is on the plus strand in the genomic sequence from 46152886 to 46160121 and encodes a primary mRNA transcript that contains 3 exons and is 6262 bp in length. Three alternative transcripts are predicted to encode the TMEM69 gene.
# Gene Neighborhood
# Function
The exact function of TMEM69 is not yet understood by the scientific community. It is, however, thought to play a role as a scaffolding protein in a G-coupled protein receptor complex in Xenopus tropicalis. It has been shown to form a cluster with the xtGPR54-2 gene IPP, and GPBP1 in scaffold_41. This complex is part of a G-coupled protein receptor which acts as the receptor for a binding ligand, kisspeptin in the plasma membrane of brain cells.
# Protein
TMEM69 is 247 amino acids in length. Five transmembrane segments are present as well as a domain of unknown function, DUF3429, which spans amino acids 91-232.
File:Features of TMEM69.jpg
## Predicted Features
Properties of TMEM69 that were predicted using Bioinformatics tools:
- Molecular Weight: 27.6 KDa.
- Isoelectric Point: 10.3
- Post-translational modification: Multiple phosphorylation sites are predicted from the NetPhos program on ExPASy . NetPhos predicted 7 for the amino acid serine at position 12, 27, 33, 85, 93, 183, and 234; 1 for threonine at position 26; and 2 for tyrosine at position 57 and 159. NetGlyc on ExPASy predicted 5 glycation sites at positions 7, 60, 73, 156, and 239.
- Transmembrane Segments: TMEM69 contains 5 transmembrane regions occurring at positions 97-117, 122-142, 159-179, 185-205, and 216-236.
# Expression
TMEM69 is expressed ubiquitously at low levels throughout the human body, although EST Profile data reveal that TMEM69 is expressed particularly high in neuroendocrine tissues such as the liver, amygdala, hippocampus, and hypothalamus. TMEM69 was found to be expressed in lower than normal values in patients suffering from atherosclerosis.
# Homology
## Orthologs
The TMEM69 gene is deeply conserved in several life forms. Although it shows highest conservation among mammalian orthologs, along with other chordates such as fish, birds, and amphibians, there is some conservation in plants, insects, fungi, and bacteria.
## Paralogs
No paralogs were found for TMEM69.
# Conservation
TMEM69 is well conserved in a variety of organisms. Although most orthologs are found in placental mammals, some orthologs are found in bacteria and fungi. The most distant ortholog found to have sequence similarity with TMEM69 is Pseudomonas putida W619, which is a type of soil bacterium. Particularly well conserved in even the most distant orthologs, including Pseudomonas putida W619, is most of the second transmembrane segment of TMEM69. In strict orthologs, all five transmembrane domains are conserved. Conserved domains found within TMEM69 are part of DUF3429, which is a family of uncharacterized proteins found in bacteria and eukaryotes. | TMEM69
TMEM69, also known as Transmembrane protein 69, is a protein that in humans is encoded by the TMEM69 gene.[1] A notable feature of the protein encoded by TMEM69 is the presence of five transmembrane segments.[2]
# Background Information
# Gene
The TMEM69 gene, located on chromosome 1p34.1, covers 7.24 kb.[3] It is on the plus strand in the genomic sequence from 46152886 to 46160121 and encodes a primary mRNA transcript that contains 3 exons and is 6262 bp in length. Three alternative transcripts are predicted to encode the TMEM69 gene.[4]
# Gene Neighborhood
# Function
The exact function of TMEM69 is not yet understood by the scientific community. It is, however, thought to play a role as a scaffolding protein in a G-coupled protein receptor complex in Xenopus tropicalis. It has been shown to form a cluster with the xtGPR54-2 gene IPP, and GPBP1 in scaffold_41.[8] This complex is part of a G-coupled protein receptor which acts as the receptor for a binding ligand, kisspeptin in the plasma membrane of brain cells.[8]
# Protein
TMEM69 is 247 amino acids in length. Five transmembrane segments are present as well as a domain of unknown function, DUF3429, which spans amino acids 91-232.[9]
File:Features of TMEM69.jpg
## Predicted Features
Properties of TMEM69 that were predicted using Bioinformatics tools:
- Molecular Weight: 27.6 KDa.[3]
- Isoelectric Point: 10.3[10]
- Post-translational modification: Multiple phosphorylation sites are predicted from the NetPhos program on ExPASy . NetPhos predicted 7 for the amino acid serine at position 12, 27, 33, 85, 93, 183, and 234; 1 for threonine at position 26; and 2 for tyrosine at position 57 and 159.[11] NetGlyc on ExPASy predicted 5 glycation sites at positions 7, 60, 73, 156, and 239.
- Transmembrane Segments: TMEM69 contains 5 transmembrane regions occurring at positions 97-117, 122-142, 159-179, 185-205, and 216-236.[12]
# Expression
TMEM69 is expressed ubiquitously at low levels throughout the human body, although EST Profile data reveal that TMEM69 is expressed particularly high in neuroendocrine tissues such as the liver, amygdala, hippocampus, and hypothalamus.[13] TMEM69 was found to be expressed in lower than normal values in patients suffering from atherosclerosis.[14]
# Homology
## Orthologs
The TMEM69 gene is deeply conserved in several life forms. Although it shows highest conservation among mammalian orthologs, along with other chordates such as fish, birds, and amphibians, there is some conservation in plants, insects, fungi, and bacteria.[9]
## Paralogs
No paralogs were found for TMEM69.
# Conservation
TMEM69 is well conserved in a variety of organisms. Although most orthologs are found in placental mammals, some orthologs are found in bacteria and fungi. The most distant ortholog found to have sequence similarity with TMEM69 is Pseudomonas putida W619, which is a type of soil bacterium.[15] Particularly well conserved in even the most distant orthologs, including Pseudomonas putida W619, is most of the second transmembrane segment of TMEM69. In strict orthologs, all five transmembrane domains are conserved.[16] Conserved domains found within TMEM69 are part of DUF3429, which is a family of uncharacterized proteins found in bacteria and eukaryotes.[9] | https://www.wikidoc.org/index.php/TMEM69 | |
3b8ed96ddd6a1637adc992983767be68bba4ee9a | wikidoc | TMEM70 | TMEM70
Transmembrane protein 70 is a protein that in humans is encoded by the TMEM70 gene. It is a transmembrane protein located in the mitochondrial inner membrane involved in the assembly of the F1 and Fo structural subunits of ATP synthase. Mutations in this gene have been associated with neonatal mitochondrial encephalo-cardiomyopathy due to ATP synthase (Complex V) deficiency, causing a wide variety of symptoms including 3-methylglutaconic aciduria, lactic acidosis, mitochondrial myopathy, and cardiomyopathy.
# Structure
The TMEM70 gene has 4 exons and is located on the q arm of chromosome 8 in position 21.11 and spans 6,642 base pairs. The gene produces a 29 kDa protein composed of 260 amino acids. The encoded protein is a multi-pass transmembrane protein localized to the mitochondrial inner membrane. It contains two putative transmembrane regions and the conserved domain DUF1301.
# Function
The encoded protein is involved in the assembly of the F1 and Fo structural subunits of ATP synthase.
# Clinical significance
Mutations in the TMEM70 gene have been associated with neonatal mitochondrial encephalocardiomyopathy due to nuclear type 2 Complex V (ATP synthase) deficiency. There are a wide variety of possible symptoms depending on the mutation, including 3-methylglutaconic aciduria, dysmorphic features, psychomotor retardation, hypotonia, growth retardation, mitochondrial myopathy and cardiomyopathy, hepatomegaly, hypoplastic kidneys, and elevated lactate levels in urine, plasma, and cerebrospinal fluid.
Most notably, a c.317-2A→G mutation in the splice site of intron 2 of this gene caused aberrant splicing and the loss of the TMEM70 transcript. This resulted in ATP synthase deficiency symptomized by apneoic spells, hypertrophic cardiomyopathy, profound lactic acidosis, hyperammonaemia, psychomotor retardation, 3-methylglutaconic aciduria, failure to thrive, and severe muscular hypotonia. Also noted in some patients were hypospadias, intrauterine growth retardation, microcephaly and cryptorchidism, but most patients did not survive the neonatal period.
Another mutation (c.366A>T) in the second exon of this gene caused an amino acid substitution (Y112X), resulting in Nuclear Type 2 Mitochondrial Complex V deficiency symptomized by lactic acidosis, psychomotor retardation, facial dysmorphism, hypertrophic cardiomyopathy, and hypospadia.
A study of mitochondrial morphology in patients with mutations in this gene revealed disorganization of the mitochondrial nucleoid. Mitochondria were abnormal, with whorled cristae and disrupted nucleoid clusters of mtDNA. The nucleoids and mitochondrial respiratory chain complexes were confined to the outer rings of the whorls.
# Interactions
The encoded protein has protein-protein interactions with RAB2A, PHC2, NDUFAF8, NDUFS5, COX6B1, ECSIT, NDUFAF4, and COA3. | TMEM70
Transmembrane protein 70 is a protein that in humans is encoded by the TMEM70 gene. It is a transmembrane protein located in the mitochondrial inner membrane involved in the assembly of the F1 and Fo structural subunits of ATP synthase.[1] Mutations in this gene have been associated with neonatal mitochondrial encephalo-cardiomyopathy due to ATP synthase (Complex V) deficiency, causing a wide variety of symptoms including 3-methylglutaconic aciduria, lactic acidosis, mitochondrial myopathy, and cardiomyopathy.[2][3]
# Structure
The TMEM70 gene has 4 exons and is located on the q arm of chromosome 8 in position 21.11 and spans 6,642 base pairs.[1] The gene produces a 29 kDa protein composed of 260 amino acids.[4][5] The encoded protein is a multi-pass transmembrane protein localized to the mitochondrial inner membrane.[6][7] It contains two putative transmembrane regions and the conserved domain DUF1301.[8][2]
# Function
The encoded protein is involved in the assembly of the F1 and Fo structural subunits of ATP synthase.[1]
# Clinical significance
Mutations in the TMEM70 gene have been associated with neonatal mitochondrial encephalocardiomyopathy due to nuclear type 2 Complex V (ATP synthase) deficiency.[1] There are a wide variety of possible symptoms depending on the mutation, including 3-methylglutaconic aciduria, dysmorphic features, psychomotor retardation, hypotonia, growth retardation, mitochondrial myopathy and cardiomyopathy, hepatomegaly, hypoplastic kidneys, and elevated lactate levels in urine, plasma, and cerebrospinal fluid.[7][3]
Most notably, a c.317-2A→G mutation in the splice site of intron 2 of this gene caused aberrant splicing and the loss of the TMEM70 transcript.[9] This resulted in ATP synthase deficiency symptomized by apneoic spells, hypertrophic cardiomyopathy, profound lactic acidosis, hyperammonaemia, psychomotor retardation, 3-methylglutaconic aciduria, failure to thrive, and severe muscular hypotonia. Also noted in some patients were hypospadias, intrauterine growth retardation, microcephaly and cryptorchidism, but most patients did not survive the neonatal period.[10]
Another mutation (c.366A>T) in the second exon of this gene caused an amino acid substitution (Y112X), resulting in Nuclear Type 2 Mitochondrial Complex V deficiency symptomized by lactic acidosis, psychomotor retardation, facial dysmorphism, hypertrophic cardiomyopathy, and hypospadia.[11][2]
A study of mitochondrial morphology in patients with mutations in this gene revealed disorganization of the mitochondrial nucleoid. Mitochondria were abnormal, with whorled cristae and disrupted nucleoid clusters of mtDNA. The nucleoids and mitochondrial respiratory chain complexes were confined to the outer rings of the whorls.[3]
# Interactions
The encoded protein has protein-protein interactions with RAB2A, PHC2, NDUFAF8, NDUFS5, COX6B1, ECSIT, NDUFAF4, and COA3.[12] | https://www.wikidoc.org/index.php/TMEM70 | |
adf1f4a16afe95d02629f0d071cae4020848b0eb | wikidoc | TMEM8A | TMEM8A
Transmembrane protein 8A is a protein that in humans is encoded by the TMEM8A gene (16p13.3.). Evolutionarily, TMEM8A orthologs are found in primates and mammals and in a few more distantly related species. TMEM8A contains five transmembrane domains and one EGF-like domain which are all highly conserved in the ortholog space. Although there is no confirmed function of TMEM8A, through analyzing expression and experimental data, it is predicted that TMEM8A is an adhesion protein that plays a role in keeping T-cells in their resting state.
# Gene
## Locus
The human gene TMEM8A is found on chromosome 16 at the band 16p13.3.
TMEM8A-gene
The span of this gene on chromosome 16 spans from base pair 420,773 to 437,113 making this gene 16,340 base pairs in length. This gene is found on the minus strand of the chromosome. There are no known isoforms.
## Aliases
TMEM8A is also known as Transmembrane protein 8A, Transmembrane Protein 6, Five-Span Transmembrane Protein M83, TMEM6, TMEM8, Transmembrane protein 8 and M83.
# Homology
## Paralogs
## Orthologs
# Protein
## Primary sequence
The gene encodes a protein also called TMEM8A. This protein in 771 amino acids in length but has been shown to have a signal peptide from amino acid 1 to 34; the mature form of the protein is only 737 amino acids in length. The precursor form with signal peptide intact has a molecular weight of 84.780 kilodaltons and the mature form with the signal peptide cleaved has a molecular weight of 81.624 kilodaltons TMEM8A has an isoelectric point of the mature form of pI=7.3.
## Domains and motifs
TMEM8A is a transmembrane protein with five transmembrane domains, making it one of only three proteins found in the human body with five domains; the other two are CD47 and AC133. The protein also contains an EGF-like domain, which is a sequence of about thirty to forty amino-acid residues, found in the sequence of epidermal growth factor (EGF), that has been shown to be present in a more or less conserved form in a large number of other, mostly animal, proteins. The functional significance of EGF domains in what appear to be unrelated proteins is not yet clear. However, a common feature is that these repeats are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted. The EGF domain includes six cysteine residues which have been shown (in EGF) to be involved in disulphide bonds. The main structure is a two-stranded beta-sheet followed by a loop to a short C-terminal two-stranded sheet. Subdomains between the conserved cysteines vary in length.
## Post-translational modifications
## Secondary Structure
# Expression
## Expression
Expression TMEM8A
TMEM8A is found to be expressed ubiquitously throughout the human body; however, it has been shown to be downregulated during CD4+ and CD8+ T-cell activation.
## Transcript variants
There are three natural transcript variants of TMEM8A. One is located at amino acid 136 where a threonine is swapped for an alanine. Another is present at amino acid 310 where an isoleucine is swapped for a valine and one at amino acid 567 where an arginine is swapped for a tryptophan. None of these variants result in a change of expression nor any loss/gain of function mutations.
# Function
# Interacting proteins
## Transcription factors
There are many predicted transcription factor binding sites in the TMEM8A promoter. Below is a table of the best possibilities, which have high confidence values, evolutionary conservation, and/or multiple possible binding sites in the promoter.
## Interactions
TMEM8A has been shown to interact with the following proteins
- ALPL
- NDUFS5
- NME4
- MACF1
- G5
- ENSG00000234651
- ENSG00000237431
- ENSG00000237495 | TMEM8A
Transmembrane protein 8A is a protein that in humans is encoded by the TMEM8A gene (16p13.3.). Evolutionarily, TMEM8A orthologs are found in primates and mammals and in a few more distantly related species. TMEM8A contains five transmembrane domains and one EGF-like domain which are all highly conserved in the ortholog space. Although there is no confirmed function of TMEM8A, through analyzing expression and experimental data, it is predicted that TMEM8A is an adhesion protein that plays a role in keeping T-cells in their resting state.
# Gene
## Locus
The human gene TMEM8A is found on chromosome 16 at the band 16p13.3.[1]
TMEM8A-gene[2]
The span of this gene on chromosome 16 spans from base pair 420,773 to 437,113 making this gene 16,340 base pairs in length. This gene is found on the minus strand of the chromosome.[3] There are no known isoforms.
## Aliases
TMEM8A is also known as Transmembrane protein 8A, Transmembrane Protein 6, Five-Span Transmembrane Protein M83, TMEM6, TMEM8, Transmembrane protein 8 and M83.[4]
# Homology
## Paralogs
## Orthologs
# Protein
## Primary sequence
The gene encodes a protein also called TMEM8A. This protein in 771 amino acids in length but has been shown to have a signal peptide from amino acid 1 to 34; the mature form of the protein is only 737 amino acids in length. The precursor form with signal peptide intact has a molecular weight of 84.780 kilodaltons and the mature form with the signal peptide cleaved has a molecular weight of 81.624 kilodaltons[6] TMEM8A has an isoelectric point of the mature form of pI=7.3.[7]
## Domains and motifs
TMEM8A is a transmembrane protein with five transmembrane domains, making it one of only three proteins found in the human body with five domains; the other two are CD47 and AC133. The protein also contains an EGF-like domain, which is a sequence of about thirty to forty amino-acid residues, found in the sequence of epidermal growth factor (EGF), that has been shown to be present in a more or less conserved form in a large number of other, mostly animal, proteins. The functional significance of EGF domains in what appear to be unrelated proteins is not yet clear. However, a common feature is that these repeats are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted. The EGF domain includes six cysteine residues which have been shown (in EGF) to be involved in disulphide bonds. The main structure is a two-stranded beta-sheet followed by a loop to a short C-terminal two-stranded sheet. Subdomains between the conserved cysteines vary in length.[8]
## Post-translational modifications
## Secondary Structure
# Expression
## Expression
Expression TMEM8A
TMEM8A is found to be expressed ubiquitously throughout the human body; however, it has been shown to be downregulated during CD4+ and CD8+ T-cell activation.[10]
## Transcript variants
There are three natural transcript variants of TMEM8A. One is located at amino acid 136 where a threonine is swapped for an alanine. Another is present at amino acid 310 where an isoleucine is swapped for a valine and one at amino acid 567 where an arginine is swapped for a tryptophan. None of these variants result in a change of expression nor any loss/gain of function mutations.[11]
# Function
# Interacting proteins
## Transcription factors
There are many predicted transcription factor binding sites in the TMEM8A promoter. Below is a table of the best possibilities, which have high confidence values, evolutionary conservation, and/or multiple possible binding sites in the promoter.
## Interactions
TMEM8A has been shown to interact with the following proteins
- ALPL
- NDUFS5
- NME4
- MACF1
- G5
- ENSG00000234651
- ENSG00000237431
- ENSG00000237495 | https://www.wikidoc.org/index.php/TMEM8A | |
100bed8a02971c56af0be0c33e05ab853e0a6539 | wikidoc | TMEM8B | TMEM8B
Transmembrane protein 8B is a protein that in humans is encoded by the TMEM8B gene. It encodes for a transmembrane protein that is 338 amino acids long, and is located on human chromosome 9. Aliases associated with this gene include C9orf127, NAG-5, and NGX61.
# Gene
## Location
Cytogenic location: 9p13.3
Located on chromosome 9 in the human genome. It starts at base pair 35,814,451, and ends at 35,865,518, and contains 19 exons. There are 13 transcript variants that are protein encoding, and the longest transcript variant is 790 amino acids long.
## Expression
Using information from NCBI’s EST Abundance Profile page on TMEM8B, expression levels vary in 32 different human tissues. The highest levels of expression can be found in the brain, ovaries, prostate, placenta, and the pancreas. Expression levels are down regulated in some cancerous tissue, specifically nasopharyngeal and colorectal carcinomas. TMEM8B is expressed in all stages of development, including fetal stages, as low levels of expression are present in the fetal liver, brain, and thymus.
# mRNA
## Splice Variants
TMEM8B has 13 known mRNA splice variants in humans: Refer to the table below. All 13 variants are protein encoding, and all contain 19 exons.
The figure below from NCBI Gene depicts the chromosomal location of each isoform in comparison to TMEM8B.
# Protein
## Protein Analysis
Protein analysis was completed on Isoform A.
TMEM8B isoform A is 472 amino acids long. The molecular weight is 36.8 kDa, and the isoelectric point is 6.773. There are 7 transmembrane domains, resulting in 52% of the protein to be within the plasma membrane. The C-charge> N-charge, and therefore the C-terminal end is on the inside. Transmembrane domains are conserved in most orthologs, including all mammals. Relative to other proteins, TMEM8B has higher than normal levels of K, Lysine, and L, Leucine. There are three repeating leucine-rich regions within conserved domains of TMEM8B, all 4 amino acids long. Leucine rich regions can result in hydrophobic interactions within themselves.
## Secondary Structure
Identifying the secondary structure is helpful in further analyzing the function of this protein. Alpha helices are the strongest indicators of transmembrane regions, as the helical structure can satisfy all backbone hydrogen-bonds internally. This is why the secondary structure of this protein is practical, as many of the alpha helices lie in the predicted transmembrane regions. Other key structures identified in this protein include extended strands, which are hypothesized to be important folding regions, and random coils, a class of conformations in the absence of a regular secondary structure.
## Tertiary Structure
I-TASSER predicted the 3D tertiary structure of TMEM8B, with strategic folding of the alpha helices and beta sheets. Although there are no high scoring hydrophobic segments of TMEM8B, that would usually be hidden within the interior of the 3D structure, the high amounts of Leuceine (L) amino acids in this protein creates hydrophobic interactions with itself, and these areas are predicted to be buried on the inside of the structure. Refer to the figure below to see a predicted tertiary structure.
TMEM8B highly resembles a tertiary structure that is similar to the Reelin protein, predicted by a 42% coverage and 14.79% identity The Reelin protein has no transmembrane domains, and is mostly found in the cerebral cortex and the hippocampus, where it plays important roles in the control of neuronal migration and formation of cellular layers during brain development.
# Homologogy
## Orthologs
The orthologs of TMEM8B were sequenced in BLAST and 20 various orthologs were picked. The orthologs are all multicellular organisms, and vary through mammals, rodents, birds, fish, amphibians, echinoderms, chordates, insects, and cnidarians. Refer to the table below. Time tree was a program that was used to find the evolutionary branching shown in MYA, and conserved domains of the genome were found and analyzed using ClustalW.
## Paralogs
One human paralog was found when this protein was sequenced in BLAST. It is 416 amino acids long, with 40% sequence identity, and 45% sequence similarity. Accision number for this protein is: NP_067082.2.
## Divergence of TMEM8B
In an evolutionary comparison of TMEM8B, one species from each group (ex. Mammals, birds, fish) was plotted to avoid overabundance of information on one graph. Also plotted the comparison of the quickly diverging cytochrome C, and slowly diverging fibrinogen. TMEM8B shows divergence somewhere in-between these two proteins.
# Clinical significance
TMEM8B shows lower expression rates in nasopharyngeal carcinomas, and expression is also down regulated in colorectal cancers. This gene also plays a negative role in an Epidermal Growth Factor Receptor (EGFR) pathway. It can delay cell cycle G0-G1 progression, and thus inhibit cell proliferation in nasopharyngeal carcinoma cells.
Mutations with this gene can be pathogenic, and cause chronic pain disorders, specifically erythromelalgia symptoms. Erythromelalgia is a rare condition that affects the extremities (hands and feet), and is characterized by intense, burning pain, severe redness, and increased skin temperature. Medications are available to reduce symptoms, however, there is no cure for this rare condition.
# Interacting Proteins
Two interacting proteins were found: EGF protein, and ATXN1L protein.
EGF plays a role in cell adhesion in nasopharyngeal carcinomas (TMEM8B also plays a role in these carcinomas). This protein is expressed on the cell surface as a glycoprotein, and ectopic induction of EGF can impair NPC cell migration and improve cell adhesion and gap junctional intercellular communication.
ATXN1L protein has a correlation with neurodegenerative disorders. Neurodegenerative disorders are characterized by a loss of balance due to the cerebellar Purkinje degeneration. Ataxia-causing proteins share interacting partners, a subset of which has been found to modify neurodegeneration in animal models. Interactome provides a tool for understanding pathogenic mechanisms common for neurodegenerative disorders. | TMEM8B
Transmembrane protein 8B is a protein that in humans is encoded by the TMEM8B gene. It encodes for a transmembrane protein that is 338 amino acids long, and is located on human chromosome 9.[1] Aliases associated with this gene include C9orf127, NAG-5, and NGX61.[2]
# Gene
## Location
Cytogenic location: 9p13.3[3]
Located on chromosome 9 in the human genome. It starts at base pair 35,814,451, and ends at 35,865,518, and contains 19 exons. There are 13 transcript variants that are protein encoding, and the longest transcript variant is 790 amino acids long.
## Expression
Using information from NCBI’s EST Abundance Profile page on TMEM8B, expression levels vary in 32 different human tissues. The highest levels of expression can be found in the brain, ovaries, prostate, placenta, and the pancreas.[4] Expression levels are down regulated in some cancerous tissue, specifically nasopharyngeal and colorectal carcinomas. TMEM8B is expressed in all stages of development, including fetal stages, as low levels of expression are present in the fetal liver, brain, and thymus.[4]
# mRNA
## Splice Variants
TMEM8B has 13 known mRNA splice variants in humans: Refer to the table below. All 13 variants are protein encoding, and all contain 19 exons.
The figure below from NCBI Gene depicts the chromosomal location of each isoform in comparison to TMEM8B.
# Protein
## Protein Analysis
Protein analysis was completed on Isoform A.
TMEM8B isoform A is 472 amino acids long. The molecular weight is 36.8 kDa,[5] and the isoelectric point is 6.773.[6] There are 7 transmembrane domains, resulting in 52% of the protein to be within the plasma membrane.[7] The C-charge> N-charge, and therefore the C-terminal end is on the inside. Transmembrane domains are conserved in most orthologs, including all mammals. Relative to other proteins, TMEM8B has higher than normal levels of K, Lysine, and L, Leucine.[5] There are three repeating leucine-rich regions within conserved domains of TMEM8B, all 4 amino acids long. Leucine rich regions can result in hydrophobic interactions within themselves.[8]
## Secondary Structure
Identifying the secondary structure is helpful in further analyzing the function of this protein. Alpha helices are the strongest indicators of transmembrane regions, as the helical structure can satisfy all backbone hydrogen-bonds internally.[9][better source needed] This is why the secondary structure of this protein is practical, as many of the alpha helices lie in the predicted transmembrane regions. Other key structures identified in this protein include extended strands, which are hypothesized to be important folding regions, and random coils, a class of conformations in the absence of a regular secondary structure.[10][better source needed]
## Tertiary Structure
I-TASSER[11] predicted the 3D tertiary structure of TMEM8B, with strategic folding of the alpha helices and beta sheets. Although there are no high scoring hydrophobic segments of TMEM8B, that would usually be hidden within the interior of the 3D structure, the high amounts of Leuceine (L) amino acids in this protein creates hydrophobic interactions with itself, and these areas are predicted to be buried on the inside of the structure.[8] Refer to the figure below to see a predicted tertiary structure.
TMEM8B highly resembles a tertiary structure that is similar to the Reelin protein, predicted by a 42% coverage and 14.79% identity[12] The Reelin protein has no transmembrane domains, and is mostly found in the cerebral cortex and the hippocampus, where it plays important roles in the control of neuronal migration and formation of cellular layers during brain development.[13][better source needed]
# Homologogy
## Orthologs
The orthologs of TMEM8B were sequenced in BLAST[14] and 20 various orthologs were picked. The orthologs are all multicellular organisms, and vary through mammals, rodents, birds, fish, amphibians, echinoderms, chordates, insects, and cnidarians. Refer to the table below. Time tree was a program that was used to find the evolutionary branching shown in MYA,[15] and conserved domains of the genome were found and analyzed using ClustalW.[16]
## Paralogs
One human paralog was found when this protein was sequenced in BLAST. It is 416 amino acids long, with 40% sequence identity, and 45% sequence similarity. Accision number for this protein is: NP_067082.2.
## Divergence of TMEM8B
In an evolutionary comparison of TMEM8B, one species from each group (ex. Mammals, birds, fish) was plotted to avoid overabundance of information on one graph. Also plotted the comparison of the quickly diverging cytochrome C, and slowly diverging fibrinogen. TMEM8B shows divergence somewhere in-between these two proteins.
# Clinical significance
TMEM8B shows lower expression rates in nasopharyngeal carcinomas, and expression is also down regulated in colorectal cancers. This gene also plays a negative role in an Epidermal Growth Factor Receptor (EGFR) pathway.[1] It can delay cell cycle G0-G1 progression, and thus inhibit cell proliferation in nasopharyngeal carcinoma cells.[1]
Mutations with this gene can be pathogenic, and cause chronic pain disorders, specifically erythromelalgia symptoms.[1][17][18] Erythromelalgia is a rare condition that affects the extremities (hands and feet), and is characterized by intense, burning pain, severe redness, and increased skin temperature.[19] Medications are available to reduce symptoms, however, there is no cure for this rare condition.[19]
# Interacting Proteins
Two interacting proteins were found: EGF protein, and ATXN1L protein.
EGF plays a role in cell adhesion in nasopharyngeal carcinomas (TMEM8B also plays a role in these carcinomas). This protein is expressed on the cell surface as a glycoprotein, and ectopic induction of EGF can impair NPC cell migration and improve cell adhesion and gap junctional intercellular communication.[20]
ATXN1L protein has a correlation with neurodegenerative disorders. Neurodegenerative disorders are characterized by a loss of balance due to the cerebellar Purkinje degeneration. Ataxia-causing proteins share interacting partners, a subset of which has been found to modify neurodegeneration in animal models. Interactome provides a tool for understanding pathogenic mechanisms common for neurodegenerative disorders.[21] | https://www.wikidoc.org/index.php/TMEM8B | |
e6fa2cb7fcd144292f859727d3fe6cb562a40fdc | wikidoc | TMEM98 | TMEM98
Transmembrane protein 98 is a single-pass membrane protein that in humans is encoded by the TMEM98 gene. The function of this protein is currently unknown. TMEM98 is also known as UNQ536/PRO1079.
# Gene
This gene is found on the plus strand of chromosome 17 at locus 17q11.2. It spans from base pairs 31,254,928 to 31,272,124.
## Variants
There are two known transcript variants that encode for TMEM98. Variant one corresponds to the longer of the two, has 8 exons, and is 1808 bases in length. Variant two codes for the same protein, but is slightly shorter at exon 2 and is missing exon 3; it is 1732 bases long. This missing region corresponds to 85 base pairs near the end of the 5' UTR. Variant one is more abundant than Variant two with 17 times the amount mRNA extracted in various human tissue experiments.
# Evolution
## Paralogs
There are no known paralogs for TMEM98. While not functional, there are two pseudogenes found on chromosome 6 and 14 in Homo sapiens.
## Orthologs
Transmembrane protein 98 is highly conserved in fish, amphibians, reptiles, birds, and other non-human mammals. It is only slightly conserved and invertebrates and insects and is not found in bacteria, archaea, protists, plants, or fungi.
## Phylogeny
The percent change over time graph was made using Time Tree.
# Protein
Transcript Variant one and two code for the same protein of 226 amino acids. The protein is 24.6 kdal with an isoelectric point of 4.26.
## Domains
There is no signal peptide in this protein. The transmembrane domain is 22 amino acids long and is located from amino acids 6-28. Amino acids on the N-terminus side are located outside of the cell, and amino acids on the C-terminius side are outside of the cell.
The paralogous domain Grap2 and cyclin-D-interacting (pfam13324) spans from 81-151 and is highly conserved in orthologs. This region is involved in the regulation of proliferation and cell differentiation using Grap2 and cyclin-d-mediated signaling pathways.
## Secondary Structure
TMEM98 is composed of 7 alpha helices as predicted by NCBI CBLAST with an e-value of 9x10−7.
# Regulation
## mRNA level
The promotor region is 901 base pairs in length. The most highly conserved predicted transcription factors are shown below.
Possible Stem Loops
The 5' UTR has two possible stem loops. These are located from 279-303 and 342-372. In the 3' UTR, there is a possible stem loop located from 1487-1502.
microRNA Binding Sites
There is one miRNA binding site in the 3' UTR as predicted using TargetScan. This miRNA, has-miR-4782-3p, may play a role in breast cancer.
## Protein level
TMEM98 has 4 predicted glycation sites at amino acids 44, 118, 120, and 133. There are serine phosphorylation sites at 60, 122, 124, 136, 145, and 191 and threonine phosphorylation sites at 55, 105, and 160. These sites are all on the N-terminus side of the transmembrane region and are inside the cytosol of the cell.
# Expression
TMEM98 is expressed highly in retina, adipose tissue, embryo, ovary, umbilical cord, uterus, prostate, large and small intestines, lung, medical olfactory epithelium, nasal organ, stomach, bladder, and adrenal gland tissues. It is expressed very low in fertilized egg, oocyte, B cell, skeletal muscle, tongue epidermis, and thymus tissues.
It is also more highly expressed later embryonic stages.
# Clinical aspects
Mutations in TMEM98 cause autosomal dominant nanophthalmos . | TMEM98
Transmembrane protein 98 is a single-pass membrane protein that in humans is encoded by the TMEM98 gene.[1][2] The function of this protein is currently unknown. TMEM98 is also known as UNQ536/PRO1079.[3]
# Gene
This gene is found on the plus strand of chromosome 17 at locus 17q11.2.[2] It spans from base pairs 31,254,928 to 31,272,124.[4]
## Variants
There are two known transcript variants that encode for TMEM98. Variant one corresponds to the longer of the two, has 8 exons, and is 1808 bases in length.[5] Variant two codes for the same protein, but is slightly shorter at exon 2 and is missing exon 3; it is 1732 bases long.[6] This missing region corresponds to 85 base pairs near the end of the 5' UTR.[6] Variant one is more abundant than Variant two with 17 times the amount mRNA extracted in various human tissue experiments.[7]
# Evolution
## Paralogs
There are no known paralogs for TMEM98.[4] While not functional, there are two pseudogenes found on chromosome 6 and 14 in Homo sapiens.[8]
## Orthologs
Transmembrane protein 98 is highly conserved in fish, amphibians, reptiles, birds, and other non-human mammals. It is only slightly conserved and invertebrates and insects and is not found in bacteria, archaea, protists, plants, or fungi.
## Phylogeny
The percent change over time graph was made using Time Tree.[9]
# Protein
Transcript Variant one and two code for the same protein of 226 amino acids.[2] The protein is 24.6 kdal with an isoelectric point of 4.26.[10]
## Domains
There is no signal peptide in this protein.[11] The transmembrane domain is 22 amino acids long and is located from amino acids 6-28. Amino acids on the N-terminus side are located outside of the cell, and amino acids on the C-terminius side are outside of the cell.[12]
The paralogous domain Grap2 and cyclin-D-interacting (pfam13324) spans from 81-151 and is highly conserved in orthologs.[13] This region is involved in the regulation of proliferation and cell differentiation using Grap2 and cyclin-d-mediated signaling pathways.[14]
## Secondary Structure
TMEM98 is composed of 7 alpha helices as predicted by NCBI CBLAST with an e-value of 9x10−7.[15]
# Regulation
## mRNA level
The promotor region is 901 base pairs in length. The most highly conserved predicted transcription factors are shown below.[16]
Possible Stem Loops
The 5' UTR has two possible stem loops. These are located from 279-303 and 342-372. In the 3' UTR, there is a possible stem loop located from 1487-1502.[17]
microRNA Binding Sites
There is one miRNA binding site in the 3' UTR as predicted using TargetScan.[18][19] This miRNA, has-miR-4782-3p, may play a role in breast cancer.[20]
## Protein level
TMEM98 has 4 predicted glycation sites at amino acids 44, 118, 120, and 133.[21] There are serine phosphorylation sites at 60, 122, 124, 136, 145, and 191 and threonine phosphorylation sites at 55, 105, and 160.[22] These sites are all on the N-terminus side of the transmembrane region and are inside the cytosol of the cell.
# Expression
TMEM98 is expressed highly in retina, adipose tissue, embryo, ovary, umbilical cord, uterus, prostate, large and small intestines, lung, medical olfactory epithelium, nasal organ, stomach, bladder, and adrenal gland tissues. It is expressed very low in fertilized egg, oocyte, B cell, skeletal muscle, tongue epidermis, and thymus tissues.
It is also more highly expressed later embryonic stages.[23]
# Clinical aspects
Mutations in TMEM98 cause autosomal dominant nanophthalmos .[24] | https://www.wikidoc.org/index.php/TMEM98 | |
a12432653947b370058bebb285516794457206eb | wikidoc | TNNI3K | TNNI3K
TNNI3 interacting kinase is a protein that in humans is encoded by the TNNI3K gene.
# Function
This gene encodes a protein that belongs to the MAP kinase kinase kinase (MAPKKK) family of protein kinases. The protein contains ankyrin repeat, protein kinase and serine-rich domains and is thought to play a role in cardiac physiology.
# Clinical significance
Mutations in TNNI3K are associated to cardiomyopathies . | TNNI3K
TNNI3 interacting kinase is a protein that in humans is encoded by the TNNI3K gene.[1]
# Function
This gene encodes a protein that belongs to the MAP kinase kinase kinase (MAPKKK) family of protein kinases. The protein contains ankyrin repeat, protein kinase and serine-rich domains and is thought to play a role in cardiac physiology.[1]
# Clinical significance
Mutations in TNNI3K are associated to cardiomyopathies .[2] | https://www.wikidoc.org/index.php/TNNI3K | |
dd4f9f5fe49dc8747107ed3038844037fd5cb68c | wikidoc | TOLLIP | TOLLIP
Toll interacting protein, also known as TOLLIP, is an inhibitory adaptor protein that in humans is encoded by the TOLLIP gene.
# Function
It is an inhibitory adaptor protein within Toll-like receptors (TLR). The TLR pathway is a part of the innate immune system that recognizes structurally conserved molecular patterns of microbial pathogens, leading to an inflammatory immune response.
# Clinical significance
Polymorphisms in TLR genes have been implicated in various diseases like atopic dermatitis. Recently, variations in the TOLLIP gene have been associated with tuberculosis and idiopathic pulmonary fibrosis.
# Interactions
TOLLIP has been shown to interact with TOM1, TLR 2, TLR 4 and IL1RAP. | TOLLIP
Toll interacting protein, also known as TOLLIP, is an inhibitory adaptor protein that in humans is encoded by the TOLLIP gene.[1][2][3]
# Function
It is an inhibitory adaptor protein within Toll-like receptors (TLR).[4] The TLR pathway is a part of the innate immune system that recognizes structurally conserved molecular patterns of microbial pathogens, leading to an inflammatory immune response.
# Clinical significance
Polymorphisms in TLR genes have been implicated in various diseases like atopic dermatitis.[5] Recently, variations in the TOLLIP gene have been associated with tuberculosis and idiopathic pulmonary fibrosis.[6][7]
# Interactions
TOLLIP has been shown to interact with TOM1,[8] TLR 2,[9] TLR 4[9] and IL1RAP.[3] | https://www.wikidoc.org/index.php/TOLLIP | |
1b10f920a67203fd87ab1d81b093f79752a755aa | wikidoc | TOMM40 | TOMM40
Translocase of outer mitochondrial membrane 40 homolog (yeast), also known as TOMM40, is a protein which in humans is encoded by the TOMM40 gene.
# Function
TOMM40 codes for a protein that is embedded into outer membranes of mitochondria and is required for the movement of proteins into mitochondria. More precisely, TOMM40 is the channel-forming subunit of a translocase of the mitochondrial outer membrane (TOM) that is essential for protein transport into mitochondria.
# Clinical significance
In humans, certain alleles of this gene have been statistically associated with an increased risk of developing late-onset Alzheimer's Disease. One study has found that TOMM40 risk alleles appears twice as often in people with Alzheimer's disease than those without it. Because TOMM40 is located on chromosome 19, and is closely adjacent to APOE, another gene known to be associated with Alzheimer's, another study has suggested that the statistically significant correlation of TOMM40 with Alzheimer's is due to linkage disequilibrium. | TOMM40
Translocase of outer mitochondrial membrane 40 homolog (yeast), also known as TOMM40, is a protein which in humans is encoded by the TOMM40 gene.[1][2]
# Function
TOMM40 codes for a protein that is embedded into outer membranes of mitochondria and is required for the movement of proteins into mitochondria. More precisely, TOMM40 is the channel-forming subunit of a translocase of the mitochondrial outer membrane (TOM) that is essential for protein transport into mitochondria.[3]
# Clinical significance
In humans, certain alleles of this gene have been statistically associated with an increased risk of developing late-onset Alzheimer's Disease.[4][5] One study has found that TOMM40 risk alleles appears twice as often in people with Alzheimer's disease than those without it.[6] Because TOMM40 is located on chromosome 19, and is closely adjacent to APOE,[2] another gene known to be associated with Alzheimer's, another study has suggested that the statistically significant correlation of TOMM40 with Alzheimer's is due to linkage disequilibrium.[7][8] | https://www.wikidoc.org/index.php/TOMM40 | |
82d54a78f101d6cbcf67816d50785fa484f0d140 | wikidoc | TOPBP1 | TOPBP1
DNA topoisomerase 2-binding protein 1 is an enzyme that in humans is encoded by the TOPBP1 gene.
# Function
This gene encodes a binding protein which interacts with the C-terminal region of topoisomerase II beta. This interaction suggests a supportive role for this protein in the catalytic reactions of topoisomerase II beta through transient breakages of DNA strands.
# Meiotic silencing
In mammals, surveillance mechanisms remove meiotic cells in which chromosome synapsis is defective. One such surveillance mechanism is meiotic silencing, the transcriptional silencing of genes on asynapsed chromosomes. TOPBP1, a DNA damage response protein, has a crucial role in meiotic sex chromosome silencing.
# Interactions
TOPBP1 has been shown to interact with:
- E2F1,
- Promyelocytic leukemia protein,
- RAD9A,
- UBR5, and
- ZBTB17
# Clinical relevance
This gene may be involved in the development of ovarian and breast cancer.
Mutations in TOPBP1 cause Idiopathic pulmonary arterial hypertension . | TOPBP1
DNA topoisomerase 2-binding protein 1 is an enzyme that in humans is encoded by the TOPBP1 gene.[1][2][3]
# Function
This gene encodes a binding protein which interacts with the C-terminal region of topoisomerase II beta. This interaction suggests a supportive role for this protein in the catalytic reactions of topoisomerase II beta through transient breakages of DNA strands.[3]
# Meiotic silencing
In mammals, surveillance mechanisms remove meiotic cells in which chromosome synapsis is defective. One such surveillance mechanism is meiotic silencing, the transcriptional silencing of genes on asynapsed chromosomes.[4] TOPBP1, a DNA damage response protein, has a crucial role in meiotic sex chromosome silencing.[4]
# Interactions
TOPBP1 has been shown to interact with:
- E2F1,[5][6]
- Promyelocytic leukemia protein,[7]
- RAD9A,[8]
- UBR5,[9] and
- ZBTB17[10]
# Clinical relevance
This gene may be involved in the development of ovarian and breast cancer.[11]
Mutations in TOPBP1 cause Idiopathic pulmonary arterial hypertension .[12] | https://www.wikidoc.org/index.php/TOPBP1 | |
499836d27a1f50d1cd5afd214c3406821a351370 | wikidoc | TP53RK | TP53RK
TP53-regulating kinase, also known as PRPK is an enzyme that in humans is encoded by the TP53RK gene. This protein is a serine/threonine protein kinase that phosphorylates p53 at Ser15.
PRPK is part of the KEOPS/EKC complex, which participates in transcription control, telomere regulation and tRNA modification.
# Model organisms
Model organisms have been used in the study of TP53RK function. A conditional knockout mouse line called Trp53rktm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping | TP53RK
TP53-regulating kinase, also known as PRPK is an enzyme that in humans is encoded by the TP53RK gene.[1][2][3] This protein is a serine/threonine protein kinase that phosphorylates p53 at Ser15.
PRPK is part of the KEOPS/EKC complex, which participates in transcription control,[4] telomere regulation [5] and tRNA modification.[6]
# Model organisms
Model organisms have been used in the study of TP53RK function. A conditional knockout mouse line called Trp53rktm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[7] Male and female animals underwent a standardized phenotypic screen[8] to determine the effects of deletion.[9][10][11][12] Additional screens performed: - In-depth immunological phenotyping[13] | https://www.wikidoc.org/index.php/TP53RK | |
a43d4d71d19ee900abaa6dbb3b2a2bc46fb3014d | wikidoc | TRAFD1 | TRAFD1
TRAF-type zinc finger domain-containing protein 1 is a protein that in humans is encoded by the TRAFD1 gene.
# Model organisms
Model organisms have been used in the study of TRAFD1 function. A conditional knockout mouse line, called Trafd1tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty eight tests were carried out on homozygous mutant mice and two significant abnormalities were observed: abnormal spine curvature and atypical peripheral blood lymphocyte parameters. | TRAFD1
TRAF-type zinc finger domain-containing protein 1 is a protein that in humans is encoded by the TRAFD1 gene.[1][2]
# Model organisms
Model organisms have been used in the study of TRAFD1 function. A conditional knockout mouse line, called Trafd1tm1a(EUCOMM)Wtsi[9][10] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[11][12][13]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[7][14] Twenty eight tests were carried out on homozygous mutant mice and two significant abnormalities were observed: abnormal spine curvature and atypical peripheral blood lymphocyte parameters.[7] | https://www.wikidoc.org/index.php/TRAFD1 | |
384e8bc770e4454f8fdcdfb274b9959e23cb5981 | wikidoc | TRDMT1 | TRDMT1
tRNA (cytosine-5-)-methyltransferase is an enzyme that in humans is encoded by the TRDMT1 gene.
CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a protein with similarity to DNA methyltransferases, but this protein does not display methyltransferase activity. The protein strongly binds DNA, suggesting that it may mark specific sequences in the genome. Alternative splicing results in multiple transcript variants encoding different isoforms.
It has been shown that human DNMT2 does not methylate DNA but instead methylates cytosine 38 in the anticodon loop of aspartic acid transfer RNA (tRNA(Asp)). | TRDMT1
tRNA (cytosine-5-)-methyltransferase is an enzyme that in humans is encoded by the TRDMT1 gene.[1][2][3][4]
CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a protein with similarity to DNA methyltransferases, but this protein does not display methyltransferase activity. The protein strongly binds DNA, suggesting that it may mark specific sequences in the genome. Alternative splicing results in multiple transcript variants encoding different isoforms.[4]
It has been shown that human DNMT2 does not methylate DNA but instead methylates cytosine 38 in the anticodon loop of aspartic acid transfer RNA (tRNA(Asp)).[5] | https://www.wikidoc.org/index.php/TRDMT1 | |
df3436a0ac4c096c033cfe08fd3c46a71710ccf1 | wikidoc | TRERF1 | TRERF1
Transcriptional-regulating factor 1 is a protein that in humans is encoded by the TRERF1 gene.
This gene encodes a zinc-finger transcriptional regulating protein that interacts with CBP/p300 to regulate the human gene CYP11A1.
# Interactions
TRERF1 has been shown to interact with Steroidogenic factor 1, EP300 and CREB-binding protein. | TRERF1
Transcriptional-regulating factor 1 is a protein that in humans is encoded by the TRERF1 gene.[1][2]
This gene encodes a zinc-finger transcriptional regulating protein that interacts with CBP/p300 to regulate the human gene CYP11A1.[2]
# Interactions
TRERF1 has been shown to interact with Steroidogenic factor 1,[3] EP300[1] and CREB-binding protein.[1] | https://www.wikidoc.org/index.php/TRERF1 | |
295710c2499c17c490aec78f49d5e38ef9238a7c | wikidoc | TRIM21 | TRIM21
Tripartite motif-containing protein 21 also known as E3 ubiquitin-protein ligase TRIM21 is a protein that in humans is encoded by the TRIM21 gene. Alternatively spliced transcript variants for this gene have been described but the full-length nature of only one has been determined. It is expressed in most human tissues.
# Structure
TRIM21 is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING finger domain, a B-box type 1 and a B-box type 2 zinc finger, and a coiled coil region.
# Function
TRIM21 is an intracellular antibody effector in the intracellular antibody-mediated proteolysis pathway. It recognizes Fc domain and binds to immunoglobulin G as well as immunoglobulin M on antibody marked non-enveloped virions which have infected the cell. Either by autoubiquitination or by ubiquitination of a cofactor, it is then responsible for directing the virions to the proteasome. TRIM21 itself is not degraded in the proteasome unlike both the viral capsid and the bound antibody.
TRIM21 is part of the RoSSA ribonucleoprotein, which includes a single polypeptide and one of four small RNA molecules. The RoSSA particle localizes to both the cytoplasm and the nucleus.
# Clinical significance
RoSSA interacts with autoantigens in patients with Sjögren's syndrome and systemic lupus erythematosus. In addition, the inability for lupus-prone macrophages to degrade immune complexes in the lysosome results in the leakage of autoantibodies into the cytosol that can bind to TRIM21 and enhance NF-κB signaling.
TRIM21 can be used to knockout specific proteins with their corresponding antibodies, a method known as Trim-Away. In this assay, TRIM21 and antibodies are delivered into cells through electroporation, and the targeted protein is degraded within a few minutes. | TRIM21
Tripartite motif-containing protein 21 also known as E3 ubiquitin-protein ligase TRIM21 is a protein that in humans is encoded by the TRIM21 gene.[1][2] Alternatively spliced transcript variants for this gene have been described but the full-length nature of only one has been determined. It is expressed in most human tissues.[3]
# Structure
TRIM21 is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING finger domain, a B-box type 1 and a B-box type 2 zinc finger, and a coiled coil region.[2]
# Function
TRIM21 is an intracellular antibody effector in the intracellular antibody-mediated proteolysis pathway. It recognizes Fc domain[4] and binds to immunoglobulin G as well as immunoglobulin M on antibody marked non-enveloped virions which have infected the cell. Either by autoubiquitination or by ubiquitination of a cofactor, it is then responsible for directing the virions to the proteasome. TRIM21 itself is not degraded in the proteasome unlike both the viral capsid and the bound antibody.[3]
TRIM21 is part of the RoSSA ribonucleoprotein, which includes a single polypeptide and one of four small RNA molecules. The RoSSA particle localizes to both the cytoplasm and the nucleus.[2]
# Clinical significance
RoSSA interacts with autoantigens in patients with Sjögren's syndrome and systemic lupus erythematosus.[2] In addition, the inability for lupus-prone macrophages to degrade immune complexes in the lysosome results in the leakage of autoantibodies into the cytosol that can bind to TRIM21 and enhance NF-κB signaling.[5]
TRIM21 can be used to knockout specific proteins with their corresponding antibodies, a method known as Trim-Away. In this assay, TRIM21 and antibodies are delivered into cells through electroporation, and the targeted protein is degraded within a few minutes.[6] | https://www.wikidoc.org/index.php/TRIM21 | |
3602551fedf1b28eda18a5f295d92ac4cc89d88b | wikidoc | TRIM22 | TRIM22
Tripartite motif-containing 22, also known as TRIM22, is a protein which in humans is encoded by the TRIM22 gene.
# Function
The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein localizes to the cytoplasm and its expression is induced by interferon. TRIM22 is also a target gene of the tumor suppressor protein p53.
TRIM22 possesses E3 ubiquitin ligase activity and is able to ubiquitinate itself with the assistance of the E2 enzyme UbcH5B. Furthermore, TRIM22 is located in the nucleus and therefore may function as a nuclear E3 ubiquitin ligase.
# Clinical significance
The protein down-regulates transcription from the HIV-1 long terminal repeat promoter region, suggesting that function of this protein may be to mediate interferon's antiviral effects. Other proteins that function to restrict HIV replication include TRIM5alpha and APOBEC3G.
It has been demonstrated that treatment of cells with interferon type I inhibits HIV replication and TRIM22 is strongly up-regulated by interferon treatment. Furthermore, HIV particle release from cells depleted of TRIM22 with RNA interference is enhanced. TRIM22 appears to prevent the movement of the HIV Gag protein to the plasma membrane and hence TRIM22 can block HIV replication in cell cultures by preventing the assembly of the virus. | TRIM22
Tripartite motif-containing 22, also known as TRIM22, is a protein which in humans is encoded by the TRIM22 gene.[1][2][3]
# Function
The protein encoded by this gene is a member of the tripartite motif (TRIM) family.[4] The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein localizes to the cytoplasm and its expression is induced by interferon.[1] TRIM22 is also a target gene of the tumor suppressor protein p53.[5]
TRIM22 possesses E3 ubiquitin ligase activity and is able to ubiquitinate itself with the assistance of the E2 enzyme UbcH5B. Furthermore, TRIM22 is located in the nucleus and therefore may function as a nuclear E3 ubiquitin ligase.[6]
# Clinical significance
The protein down-regulates transcription from the HIV-1 long terminal repeat promoter region, suggesting that function of this protein may be to mediate interferon's antiviral effects.[1][2] Other proteins that function to restrict HIV replication include TRIM5alpha and APOBEC3G.[7]
It has been demonstrated that treatment of cells with interferon type I inhibits HIV replication and TRIM22 is strongly up-regulated by interferon treatment. Furthermore, HIV particle release from cells depleted of TRIM22 with RNA interference is enhanced. TRIM22 appears to prevent the movement of the HIV Gag protein to the plasma membrane and hence TRIM22 can block HIV replication in cell cultures by preventing the assembly of the virus.[8][9] | https://www.wikidoc.org/index.php/TRIM22 | |
dbbb5477f10fd121eb2430c45580803d351889b4 | wikidoc | TRIM23 | TRIM23
GTP-binding protein ARD-1 is a protein that in humans is encoded by the TRIM23 gene.
# Function
The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein is also a member of the ADP ribosylation factor family of guanine nucleotide-binding family of proteins. Its carboxy terminus contains an ADP-ribosylation factor domain and a guanine nucleotide binding site, while the amino terminus contains a GTPase activating protein domain which acts on the guanine nucleotide binding site. The protein localizes to lysosomes and the Golgi apparatus. It plays a role in the formation of intracellular transport vesicles, their movement from one compartment to another, and phospholipase D activation. Three alternatively spliced transcript variants for this gene have been described.
# Interactions
TRIM23 has been shown to interact with TRIM31, TRIM29 and PSCD1. | TRIM23
GTP-binding protein ARD-1 is a protein that in humans is encoded by the TRIM23 gene.[1][2]
# Function
The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein is also a member of the ADP ribosylation factor family of guanine nucleotide-binding family of proteins. Its carboxy terminus contains an ADP-ribosylation factor domain and a guanine nucleotide binding site, while the amino terminus contains a GTPase activating protein domain which acts on the guanine nucleotide binding site. The protein localizes to lysosomes and the Golgi apparatus. It plays a role in the formation of intracellular transport vesicles, their movement from one compartment to another, and phospholipase D activation. Three alternatively spliced transcript variants for this gene have been described.[2]
# Interactions
TRIM23 has been shown to interact with TRIM31,[3] TRIM29[3] and PSCD1.[4] | https://www.wikidoc.org/index.php/TRIM23 | |
df505d6d87cecf1ec7259c264c68a21f837b37f1 | wikidoc | TRIM24 | TRIM24
Tripartite motif-containing 24 (TRIM24) also known as transcriptional intermediary factor 1α (TIF1α) is a protein that, in humans, is encoded by the TRIM24 gene.
# Function
The protein encoded by this gene mediates transcriptional control by interaction with the activation function 2 (AF2) region of several nuclear receptors, including the estrogen, retinoic acid, and vitamin D3 receptors. The protein localizes to nuclear bodies and is thought to associate with chromatin and heterochromatin-associated factors. The protein is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains – a RING, a B-box type 1 and a B-box type 2 – and a coiled-coil region. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene.
# Interactions
TRIM24 has been shown to interact with Mineralocorticoid receptor, TRIM33, Estrogen receptor alpha and Retinoid X receptor alpha. | TRIM24
Tripartite motif-containing 24 (TRIM24) also known as transcriptional intermediary factor 1α (TIF1α) is a protein that, in humans, is encoded by the TRIM24 gene.[1][2][3]
# Function
The protein encoded by this gene mediates transcriptional control by interaction with the activation function 2 (AF2) region of several nuclear receptors, including the estrogen, retinoic acid, and vitamin D3 receptors. The protein localizes to nuclear bodies and is thought to associate with chromatin and heterochromatin-associated factors. The protein is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains – a RING, a B-box type 1 and a B-box type 2 – and a coiled-coil region. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene.[1]
# Interactions
TRIM24 has been shown to interact with Mineralocorticoid receptor,[2][4] TRIM33,[5] Estrogen receptor alpha[2][6] and Retinoid X receptor alpha.[2][7] | https://www.wikidoc.org/index.php/TRIM24 | |
6f2a6bb6d5804927119579076f43988bb9dfe1bb | wikidoc | TRIM25 | TRIM25
Tripartite motif-containing protein 25 is a protein that in humans is encoded by the TRIM25 gene.
# Function
The protein encoded by this gene is a member of the tripartite motif (TRIM) family grouping more than 70 TRIMs. TRIM proteins primarily function as ubiquitin ligases that regulate the innate response to infection. TRIM25 localizes to the cytoplasm. The presence of potential DNA-binding and dimerization-transactivation domains suggests that this protein may act as a transcription factor, similar to several other members of the TRIM family. Expression of the gene is upregulated in response to estrogen, and it is thought to mediate estrogen actions in breast cancer as a primary response gene.
# Domain Architecture
TRIM25 has an N-terminal RING domain, followed by a B-box type 1 domain, a B-box type 2 domain, a coiled-coil domain (CCD) and a C-terminal SPRY domain. The RING domain coordinates two zinc atoms and is essential for recruiting ubiquitin-conjugating enzymes. The function of the B-box domains is unknown. The CCD domain has been implicated in multimerization and other protein-protein interactions. The SPRY domain is required for substrate recruitment. The NMR chemical shifts for backbone of the PRYSPRY domain of TRIM25 is assigned based on triple-resonance experiments using uniformly isotopic labeled protein and the secondary structure of the domain PRYSPRY domain of TRIM25 predicted based on the NMR assignments.
# TRIM25 functions
TRIM25 plays a key role in the RIG-I signaling pathway. RIG-I is a cytosolic pattern recognition receptor that senses viral RNA. Following RNA recognition, the caspase recruitment domain (CARD) of RIG-I undergoes K(63)-linked ubiquitination by TRIM25. The RING and SPRY domains of TRIM25 mediate its interaction with RIG-I. IFN production then follows by an intracellular signaling pathway involving IRF3.
# Viral escape
To avoid IFN production, the non structural protein (NS1) of influenza will interact with CCD domain of TRIM25 to block RIG-I ubiquitination. Some studies have shown that a deletion of the CCD domain of TRIM25 prevents the binding of NS1. Without this ubiquitination, there won’t be IFN production. | TRIM25
Tripartite motif-containing protein 25 is a protein that in humans is encoded by the TRIM25 gene.[1][2]
# Function
The protein encoded by this gene is a member of the tripartite motif (TRIM) family grouping more than 70 TRIMs. TRIM proteins primarily function as ubiquitin ligases that regulate the innate response to infection.[3] TRIM25 localizes to the cytoplasm. The presence of potential DNA-binding and dimerization-transactivation domains suggests that this protein may act as a transcription factor, similar to several other members of the TRIM family. Expression of the gene is upregulated in response to estrogen, and it is thought to mediate estrogen actions in breast cancer as a primary response gene.[2]
# Domain Architecture
TRIM25 has an N-terminal RING domain, followed by a B-box type 1 domain, a B-box type 2 domain, a coiled-coil domain (CCD) and a C-terminal SPRY domain. The RING domain coordinates two zinc atoms and is essential for recruiting ubiquitin-conjugating enzymes. The function of the B-box domains is unknown. The CCD domain has been implicated in multimerization and other protein-protein interactions.[4] The SPRY domain is required for substrate recruitment.[5] The NMR chemical shifts for backbone of the PRYSPRY domain of TRIM25 is assigned based on triple-resonance experiments using uniformly isotopic labeled protein and the secondary structure of the domain PRYSPRY domain of TRIM25 predicted based on the NMR assignments.[6]
# TRIM25 functions
TRIM25 plays a key role in the RIG-I signaling pathway. RIG-I is a cytosolic pattern recognition receptor that senses viral RNA. Following RNA recognition, the caspase recruitment domain (CARD) of RIG-I undergoes K(63)-linked ubiquitination by TRIM25. The RING and SPRY domains of TRIM25 mediate its interaction with RIG-I. IFN production then follows by an intracellular signaling pathway involving IRF3.[7]
# Viral escape
To avoid IFN production, the non structural protein (NS1) of influenza will interact with CCD domain of TRIM25 to block RIG-I ubiquitination. Some studies have shown that a deletion of the CCD domain of TRIM25 prevents the binding of NS1.[8] Without this ubiquitination, there won’t be IFN production. | https://www.wikidoc.org/index.php/TRIM25 | |
ceb258f00faebfe9eafb982b9fb444b9e0e31444 | wikidoc | TRIM28 | TRIM28
Tripartite motif-containing 28 (TRIM28), also known as transcriptional intermediary factor 1β (TIF1β) and KAP1 (KRAB-associated protein-1), is a protein that in humans is encoded by the TRIM28 gene.
# Function
The protein encoded by this gene mediates transcriptional control by interaction with the Krüppel-associated box repression domain found in many transcription factors. The protein localizes to the nucleus and is thought to associate with specific chromatin regions. The protein is a member of the tripartite motif family. This tripartite motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region.
KAP1 is a ubiquitously expressed protein involved in many critical functions including: transcriptional regulation, cellular differentiation and proliferation, DNA damage repair, viral suppression, and apoptosis.(4) Its functionality is dependent upon post-translational modifications. Phosphorylation of KAP1 acts as a deactivator of the protein in many of its mechanisms while sumoylation acts as an activator.
## Cellular differentiation and proliferation
Studies have shown that deletion of KAP1 in mice before gastrulation results in death (implicating it as a necessary protein for proliferation) while deletion in adult mice results in increased anxiety and stress-induced alterations in learning and memory. KAP1 has been shown to participate in the maintenance of pluripotency of embryonic stem cells and to promote and inhibit cellular differentiation of adult cell lines. Increased levels of KAP1 have been found in liver, gastric, breast, lung, and prostate cancers as well, indicating that it may play an important role in tumor cell proliferation (possibly by inhibiting apoptosis).
## Transcriptional regulation
KAP1 can regulate genomic transcription through a variety of mechanisms, many of which remain somewhat unclear. Studies have shown that KAP1 can repress transcription by binding directly to the genome (which can be sufficient in and of itself) or through the induction of heterochromatin formation via the Mi2α-SETB1-HP1 macromolecular complex. KAP1 can also interact with histone methyltransferases and deacetylases via the C-terminal PHD and Bromodomain to control transcription epigenetically.
## DNA damage repair response
It has been shown that ATM phosphorylates KAP1 upon the discovery of damaged or broken DNA. Phosphorylated KAP1, along with many other DNA damage proteins, rapidly migrate to the site of the DNA damage. Its exact involvement in this pathway is somewhat unclear, but it has been implicated in triggering cell arrest, allowing for the damaged DNA to be repaired.
## Apoptosis
KAP1 forms a complex with MDM2 (a ubiquitin E3 ligase) that binds to p53. The complex marks the bound p53 for degradation. p53 is a known precursor of apoptosis that facilitates the synthesis of proteins necessary for cell death so its degradation results in apoptosis inhibition.
# Clinical significance
## Role in the establishment of viral latency
KAP1 facilitates the establishment of viral latency in certain cell types for Human Cytomegalovirus (HCMV) and other endogenous retroviruses
. KAP1 acts as a transcriptional corepressor of the viral genome. The protein binds to the histones of the viral chromatin and then recruits Mi2α and SETB1. SETB1 is a histone methyltransferase that recruits HP1, thus inducing heterochromatin formation. This heterochromatin formation prevents the transcription of the viral genome. mTOR has been implicated in the phosphorylation of KAP1 resulting in a switch from latency to the lytic cycle.
## Manipulations and potential for future treatment
Ataxia telangiectasia mutated (ATM) is a kinase that (similar to mTOR) can phosphorylate KAP1 resulting in the switch from viral latency to the lytic cycle. Chloroquine (an ATM) activator has been shown to result in increases in transcription of the HCMV genome. This effect is augmented by the use of tumor necrosis factor It has been proposed that this treatment (accompanied by antiretroviral treatment) has the potential to purge the virus from infected individuals.
# Interactions
TRIM28 has been shown to interact with:
- CBX5,
- CEBPB,
- Glucocorticoid receptor,
- SETDB1 and
- ZNF10. | TRIM28
Tripartite motif-containing 28 (TRIM28), also known as transcriptional intermediary factor 1β (TIF1β) and KAP1 (KRAB-associated protein-1), is a protein that in humans is encoded by the TRIM28 gene.[1][2]
# Function
The protein encoded by this gene mediates transcriptional control by interaction with the Krüppel-associated box repression domain found in many transcription factors. The protein localizes to the nucleus and is thought to associate with specific chromatin regions. The protein is a member of the tripartite motif family. This tripartite motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region.[3]
KAP1 is a ubiquitously expressed protein involved in many critical functions including: transcriptional regulation, cellular differentiation and proliferation, DNA damage repair, viral suppression, and apoptosis.(4) Its functionality is dependent upon post-translational modifications. Phosphorylation of KAP1 acts as a deactivator of the protein in many of its mechanisms while sumoylation acts as an activator.[4]
## Cellular differentiation and proliferation
Studies have shown that deletion of KAP1 in mice before gastrulation results in death (implicating it as a necessary protein for proliferation) while deletion in adult mice results in increased anxiety and stress-induced alterations in learning and memory. KAP1 has been shown to participate in the maintenance of pluripotency of embryonic stem cells and to promote and inhibit cellular differentiation of adult cell lines. Increased levels of KAP1 have been found in liver, gastric, breast, lung, and prostate cancers as well, indicating that it may play an important role in tumor cell proliferation (possibly by inhibiting apoptosis).[4]
## Transcriptional regulation
KAP1 can regulate genomic transcription through a variety of mechanisms, many of which remain somewhat unclear. Studies have shown that KAP1 can repress transcription by binding directly to the genome (which can be sufficient in and of itself) or through the induction of heterochromatin formation via the Mi2α-SETB1-HP1 macromolecular complex.[5][6] KAP1 can also interact with histone methyltransferases and deacetylases via the C-terminal PHD and Bromodomain to control transcription epigenetically.[4]
## DNA damage repair response
It has been shown that ATM phosphorylates KAP1 upon the discovery of damaged or broken DNA. Phosphorylated KAP1, along with many other DNA damage proteins, rapidly migrate to the site of the DNA damage. Its exact involvement in this pathway is somewhat unclear, but it has been implicated in triggering cell arrest, allowing for the damaged DNA to be repaired.[4]
## Apoptosis
KAP1 forms a complex with MDM2 (a ubiquitin E3 ligase) that binds to p53. The complex marks the bound p53 for degradation. p53 is a known precursor of apoptosis that facilitates the synthesis of proteins necessary for cell death so its degradation results in apoptosis inhibition.[4]
# Clinical significance
## Role in the establishment of viral latency
KAP1 facilitates the establishment of viral latency in certain cell types for Human Cytomegalovirus (HCMV) and other endogenous retroviruses[4][5]
. KAP1 acts as a transcriptional corepressor of the viral genome. The protein binds to the histones of the viral chromatin and then recruits Mi2α and SETB1. SETB1 is a histone methyltransferase that recruits HP1, thus inducing heterochromatin formation. This heterochromatin formation prevents the transcription of the viral genome. mTOR has been implicated in the phosphorylation of KAP1 resulting in a switch from latency to the lytic cycle.[5]
## Manipulations and potential for future treatment
Ataxia telangiectasia mutated (ATM) is a kinase that (similar to mTOR) can phosphorylate KAP1 resulting in the switch from viral latency to the lytic cycle. Chloroquine (an ATM) activator has been shown to result in increases in transcription of the HCMV genome. This effect is augmented by the use of tumor necrosis factor It has been proposed that this treatment (accompanied by antiretroviral treatment) has the potential to purge the virus from infected individuals.[5]
# Interactions
TRIM28 has been shown to interact with:
- CBX5,[7][8][9][10]
- CEBPB,[11]
- Glucocorticoid receptor,[11]
- SETDB1[12] and
- ZNF10.[13][14] | https://www.wikidoc.org/index.php/TRIM28 | |
27b448ab6bd9ab3af408841df6891daad2f64295 | wikidoc | TRIM32 | TRIM32
Tripartite motif-containing protein 32 is a protein that in humans is encoded by the TRIM32 gene. Since its discovery in 1995, TRIM32 has been shown to be implicated in a number of diverse biological pathways.
# Structure
The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region.
# Subcellular distribution
The protein localizes to cytoplasmic bodies. The protein has also been localized to the nucleus, where it interacts with the activation domain of the HIV-1 Tat protein. The Tat protein activates transcription of HIV-1 genes.
# Interactions
TRIM32 has been shown to interact with:
- actin,
- ABI2
- c-Myc,
- dysbindin, and
- piasy,
# Function
## Mechanism
Currently, TRIM32 is believed to employ two different mechanisms to affect molecular targets. First, it can act through its N-terminal RING finger as an E3 ubiquitin ligase, responsible for attaching ubiquitin molecules to lysine residues of target proteins, in order to mark them for proteosome degradation. Currently evidence suggests TRIM32 ubiquitinates multiple proteins including c-Myc, dysbindin, actin, piasy, and Abl-interactor2 (ABI2). The second mechanism by which TRIM32 is believed to operate involves binding of proteins to the C-terminal NHL repeat, which has been shown to activate miRNAs.
## Development
Research has recently shown the importance of TRIM32 in the development of the mouse neocortex. In the mouse neocortex, neural progenitor cells generate daughter cells which either differentiate into specific neurons or maintain the progenitor state of the mother cell. TRIM32 helps control the balance between differentiating and progenitor cells by localizing to a pole during progenitor cell division, and thus becoming concentrated in one of the two daughter cells. This asymmetric division of TRIM32 induces neuronal differentiation in daughter cells which contain high TRIM32 concentrations, while cells with low TRIM32 concentrations retain progenitor cell fate. Proposed theories on how TRIM32 induces differentiation involve the ubiquitination of the transcription factor c-Myc and the binding of Argonaute-1 (Ago-1). The binding of Ago-1 induces activity of miRNAs, particularly Let-7a, which has been shown to play a role in regulating proliferation and neuronal differentiation.
## Skeletal muscle
TRIM32 is expressed in skeletal muscle, where it interacts with myosin and may ubiquitinate actin (it has been shown to do so in vitro). No difference has been observed between wild-type and LHMD2H-mutated TRIM32 in terms of actin or myosin binding, however, and thus the mechanism which causes the muscular dystrophy, LGMD2H, is still unknown. Additionally, TRIM32 is known to ubiquitinate dysbindin, a protein associated with both skeletal muscles and neural tissue. The purpose and effects of the ubiquitination of dysbindin are as yet unclear.
# Clinical significance
## Mutation-associated diseases
Bardet–Biedl syndrome (BBS): TRIM32 is one of 14
genes known to be linked with BBS. Specifically a mutation (P130S) in the B-box of TRIM32 gives rise to BBS.
Limb-girdle muscular dystrophy type2H (LGMD2H): LGMD2H is caused by 4 mutations of TRIM32 in the C-terminal NHL domain: D487N (third NHL repeat), R394H (first NHL repeat), T520TfsX13 (fourth NHL repeat), and D588del (fifth NHL repeat).
## Cancer
TRIM32 is overexpressed in skin cancer cells. It is thought that TRIM32 regulates NF-κB activity through ubiquitination of Protein Inhibitor of Activated STAT Y (Piasy). Piasy acts as an inhibitor of NF-κB, and NF-κB acts as an anti-apoptotic factor. Thus, when Piasy is present, NF-κB is inhibited, and keratinocytes undergo apoptosis when exposed to ultraviolet-B radiation or TNFα, preventing cancer formation. When TRIM32 is overexpressed, Piasy is degraded, allowing NF-κB to function, and thus when cells are exposed to ultraviolet-B radiation or TNFα, apoptosis does not occur, potentially allowing cancer formation.
TRIM32 additionally promotes cancer formation by ubiquitinating Abl-interactor 2 (Abi2), which is a tumor suppressor and inhibitor of cell migration. | TRIM32
Tripartite motif-containing protein 32 is a protein that in humans is encoded by the TRIM32 gene.[1][2][3][4] Since its discovery in 1995, TRIM32 has been shown to be implicated in a number of diverse biological pathways.
# Structure
The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region.[4]
# Subcellular distribution
The protein localizes to cytoplasmic bodies. The protein has also been localized to the nucleus, where it interacts with the activation domain of the HIV-1 Tat protein. The Tat protein activates transcription of HIV-1 genes.[4]
# Interactions
TRIM32 has been shown to interact with:
- actin,[5]
- ABI2[6]
- c-Myc,[7]
- dysbindin,[8] and
- piasy,[9]
# Function
## Mechanism
Currently, TRIM32 is believed to employ two different mechanisms to affect molecular targets. First, it can act through its N-terminal RING finger as an E3 ubiquitin ligase, responsible for attaching ubiquitin molecules to lysine residues of target proteins, in order to mark them for proteosome degradation. Currently evidence suggests TRIM32 ubiquitinates multiple proteins including c-Myc, dysbindin, actin, piasy, and Abl-interactor2 (ABI2). The second mechanism by which TRIM32 is believed to operate involves binding of proteins to the C-terminal NHL repeat, which has been shown to activate miRNAs.[7]
## Development
Research has recently shown the importance of TRIM32 in the development of the mouse neocortex. In the mouse neocortex, neural progenitor cells generate daughter cells which either differentiate into specific neurons or maintain the progenitor state of the mother cell. TRIM32 helps control the balance between differentiating and progenitor cells by localizing to a pole during progenitor cell division, and thus becoming concentrated in one of the two daughter cells. This asymmetric division of TRIM32 induces neuronal differentiation in daughter cells which contain high TRIM32 concentrations, while cells with low TRIM32 concentrations retain progenitor cell fate. Proposed theories on how TRIM32 induces differentiation involve the ubiquitination of the transcription factor c-Myc and the binding of Argonaute-1 (Ago-1). The binding of Ago-1 induces activity of miRNAs, particularly Let-7a, which has been shown to play a role in regulating proliferation and neuronal differentiation.[7]
## Skeletal muscle
TRIM32 is expressed in skeletal muscle, where it interacts with myosin and may ubiquitinate actin (it has been shown to do so in vitro).[5] No difference has been observed between wild-type and LHMD2H-mutated TRIM32 in terms of actin or myosin binding, however, and thus the mechanism which causes the muscular dystrophy, LGMD2H, is still unknown.[10] Additionally, TRIM32 is known to ubiquitinate dysbindin, a protein associated with both skeletal muscles and neural tissue. The purpose and effects of the ubiquitination of dysbindin are as yet unclear.[8]
# Clinical significance
## Mutation-associated diseases
Bardet–Biedl syndrome (BBS): TRIM32 is one of 14[11]
genes known to be linked with BBS. Specifically a mutation (P130S) in the B-box of TRIM32 gives rise to BBS.[8]
Limb-girdle muscular dystrophy type2H (LGMD2H): LGMD2H is caused by 4 mutations of TRIM32 in the C-terminal NHL domain: D487N (third NHL repeat), R394H (first NHL repeat), T520TfsX13 (fourth NHL repeat), and D588del (fifth NHL repeat).[8]
## Cancer
TRIM32 is overexpressed in skin cancer cells. It is thought that TRIM32 regulates NF-κB activity through ubiquitination of Protein Inhibitor of Activated STAT Y (Piasy).[9] Piasy acts as an inhibitor of NF-κB, and NF-κB acts as an anti-apoptotic factor. Thus, when Piasy is present, NF-κB is inhibited, and keratinocytes undergo apoptosis when exposed to ultraviolet-B radiation or TNFα, preventing cancer formation. When TRIM32 is overexpressed, Piasy is degraded, allowing NF-κB to function, and thus when cells are exposed to ultraviolet-B radiation or TNFα, apoptosis does not occur, potentially allowing cancer formation.[10]
TRIM32 additionally promotes cancer formation by ubiquitinating Abl-interactor 2 (Abi2), which is a tumor suppressor and inhibitor of cell migration.[9] | https://www.wikidoc.org/index.php/TRIM32 | |
06c14cd02c9f1033f7866d5d366d54ffba0d0b33 | wikidoc | TRIM33 | TRIM33
Tripartite motif-containing 33 (TRIM33) also known as transcriptional intermediary factor 1 gamma (TIF1-γ), is a human gene.
The protein encoded by this gene is thought to be a transcriptional corepressor. However unlike the related TIF1-α and TIF1-β proteins, few transcription factors such as Smad4 that interact with TIF1-γ have been identified.
# Structure
The protein is a member of the tripartite motif family. This motif includes three zinc-binding domains:
- RING
- B-box type 1 zinc finger
- B-box type 2 zinc finger
and a coiled-coil region.
Three alternatively spliced transcript variants for this gene have been described, however, the full-length nature of one variant has not been determined.
# Interactions
TRIM33 has been shown to interact with TRIM24.
# Role in cancer
TRIM33 acts as a tumor suppressor gene preventing the development chronic myelomonocytic leukemia.
TRIM33 regulates also the TGF-β1 receptor and promotes physiological aging of hematopoietic stem cells.
TRIM33 acts as an oncogene by preventing apoptosis in B-cell leukemias. | TRIM33
Tripartite motif-containing 33 (TRIM33) also known as transcriptional intermediary factor 1 gamma (TIF1-γ), is a human gene.[1][2]
The protein encoded by this gene is thought to be a transcriptional corepressor. However unlike the related TIF1-α and TIF1-β proteins, few transcription factors such as Smad4 that interact with TIF1-γ have been identified.[1]
# Structure
The protein is a member of the tripartite motif family.[3] This motif includes three zinc-binding domains:
- RING
- B-box type 1 zinc finger
- B-box type 2 zinc finger
and a coiled-coil region.
Three alternatively spliced transcript variants for this gene have been described, however, the full-length nature of one variant has not been determined.[1]
# Interactions
TRIM33 has been shown to interact with TRIM24.[4]
# Role in cancer
TRIM33 acts as a tumor suppressor gene preventing the development chronic myelomonocytic leukemia.[5]
TRIM33 regulates also the TGF-β1 receptor and promotes physiological aging of hematopoietic stem cells.
[6]
TRIM33 acts as an oncogene by preventing apoptosis in B-cell leukemias.[7] | https://www.wikidoc.org/index.php/TRIM33 | |
0906902f23fd4604e72bba87e55193dc4c1139b6 | wikidoc | TRIM45 | TRIM45
tripartite motif containing 45, also known as TRIM45, is a human gene.
This gene encodes a member of the tripartite motif family. The encoded protein may function as a
# Model organisms
Model organisms have been used in the study of TRIM45 function. A conditional knockout mouse line, called Trim45tm1a(KOMP)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty six tests were carried out on mutant mice and three significant abnormalities were observed. No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; males had increased circulating magnesium levels while animals of both sex displayed increased bone strength. | TRIM45
tripartite motif containing 45, also known as TRIM45, is a human gene.[1]
This gene encodes a member of the tripartite motif family. The encoded protein may function as a [transcriptional repressor of the mitogen-activated protein kinase pathway. Alternatively spliced transcript variants have been described.[1]
# Model organisms
Model organisms have been used in the study of TRIM45 function. A conditional knockout mouse line, called Trim45tm1a(KOMP)Wtsi[7][8] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[9][10][11]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[5][12] Twenty six tests were carried out on mutant mice and three significant abnormalities were observed.[5] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; males had increased circulating magnesium levels while animals of both sex displayed increased bone strength.[5] | https://www.wikidoc.org/index.php/TRIM45 | |
8e288ef9098e5b0f1cbdbc01eaaba7918179299d | wikidoc | TRIM63 | TRIM63
E3 ubiquitin-protein ligase TRIM63 is an enzyme that in humans is encoded by the TRIM63 gene.
This gene encodes a member of the RING zinc finger protein family found in striated muscle and iris. The product of this gene is localized to the Z-line and M-line lattices of myofibrils, where titin's N-terminal and C-terminal regions respectively bind to the sarcomere. In vitro binding studies have shown that this protein also binds directly to titin near the region of titin containing kinase activity. Another member of this protein family binds to microtubules. Since these family members can form heterodimers, this suggests that these proteins may serve as a link between titin kinase and microtubule-dependent signal pathways in muscle.
The protein encoded by the Trim63 gene is also called MuRF1. MuRF1 is the name most commonly used in the literature, and it stands for "Muscle RING Finger 1." Structurally, there are two closely related MuRFs, MuRF2 and MuRF3. These also have TRIM codes: MuRF2 is TRIM55; MuRF3 is TRIM54.
# Interactions
Trim63/MuRF1 has been shown to be an E3 ubiquitin ligase. It's major substrate is Myosin Heavy Chain. MuRF1 is upregulated during skeletal muscle atrophy - and thus the degradation of myosin heavy chain, which is a major component of the sarcomere, is an important mechanism in the breakdown of skeletal muscle under atrophy conditions. MuRF1 has been shown to be upregulated during denervation, administration of glucocorticods, immobilization, and casting. All of these treatments cause skeletal muscle atrophy.
TRIM63 has been shown to interact with Titin, GMEB1 and SUMO2. | TRIM63
E3 ubiquitin-protein ligase TRIM63 is an enzyme that in humans is encoded by the TRIM63 gene.[1][2][3]
This gene encodes a member of the RING zinc finger protein family found in striated muscle and iris. The product of this gene is localized to the Z-line and M-line lattices of myofibrils, where titin's N-terminal and C-terminal regions respectively bind to the sarcomere. In vitro binding studies have shown that this protein also binds directly to titin near the region of titin containing kinase activity. Another member of this protein family binds to microtubules. Since these family members can form heterodimers, this suggests that these proteins may serve as a link between titin kinase and microtubule-dependent signal pathways in muscle.[3]
The protein encoded by the Trim63 gene is also called MuRF1. MuRF1 is the name most commonly used in the literature, and it stands for "Muscle RING Finger 1." Structurally, there are two closely related MuRFs, MuRF2 and MuRF3. These also have TRIM codes: MuRF2 is TRIM55; MuRF3 is TRIM54.
# Interactions
Trim63/MuRF1 has been shown to be an E3 ubiquitin ligase. It's major substrate is Myosin Heavy Chain. MuRF1 is upregulated during skeletal muscle atrophy - and thus the degradation of myosin heavy chain, which is a major component of the sarcomere, is an important mechanism in the breakdown of skeletal muscle under atrophy conditions. MuRF1 has been shown to be upregulated during denervation, administration of glucocorticods, immobilization, and casting. All of these treatments cause skeletal muscle atrophy.
TRIM63 has been shown to interact with Titin,[1] GMEB1[4] and SUMO2.[2] | https://www.wikidoc.org/index.php/TRIM63 | |
cac97ae8c9a9c1f0ce9d2c6a99c7b9af1fb89293 | wikidoc | TRIP11 | TRIP11
Thyroid receptor-interacting protein 11 is a protein that in humans is encoded by the TRIP11 gene.
# Function
TRIP11 was first identified through its ability to interact functionally with thyroid hormone receptor-beta (THRB; MIM 190160). It has also been found in association with the Golgi apparatus and microtubules.
# Interactions
TRIP11 has been shown to interact with Retinoblastoma protein and Thyroid hormone receptor alpha. | TRIP11
Thyroid receptor-interacting protein 11 is a protein that in humans is encoded by the TRIP11 gene.[1][2][3]
# Function
TRIP11 was first identified through its ability to interact functionally with thyroid hormone receptor-beta (THRB; MIM 190160). It has also been found in association with the Golgi apparatus and microtubules.[supplied by OMIM][3]
# Interactions
TRIP11 has been shown to interact with Retinoblastoma protein[4] and Thyroid hormone receptor alpha.[4] | https://www.wikidoc.org/index.php/TRIP11 | |
9ad9822bf720475a2b203691ca6c575b5c6dd586 | wikidoc | TRIP13 | TRIP13
TRIP13 is a mammalian gene that encodes the thyroid receptor-interacting protein 13. In budding yeast, the analog for TRIP13 is PCH2. TRIP13 is a member of the AAA+ ATPase family, a family known for mechanical forces derived from ATP hydrolase reactions. The TRIP13 gene has been shown to interact with a variety of proteins and implicated in a few diseases, notably interacting with the ligand binding domain of thyroid hormone receptors, and may play a role in early-stage non-small cell lung cancer. However, recent evidence implicates TRIP13 in various cell cycle phases, including meiosis G2/Prophase and during the Spindle Assembly checkpoint (SAC). Evidence shows regulation to occur through the HORMA domains, including Hop1, Rev7, and Mad2. Of note, Mad2's involvement in the SAC is shown to be affected by TRIP13 Due to TRIP13's role in cell cycle arrest and progression, it may present opportunity as a therapeutic candidate for cancers.
# Structure
As an AAA+ ATPase, TRIP13 (and its PCH2 analog) forms homohexamers and interacts with ATP as an energy source. With respect to Hop1, PCH2 binds to and structurally changes Hop1, displacing the Hop1 from DNA. TRIP13/PCH2 interacts with ATP as a hydrolase, hydrolyzing phosphates to derive energy for conformational changes that can induce mechanical force on its substrate, Hop1 in the previous case. TRIP14/PCH2 is believed to have a single AAA+ ATPase domain. TRIP13/PCH2 also functions as a kinetochore protein that interacts with the silencing protein p31-Comet.
# Role in meiosis G2/prophase
Meiosis in mammalian cells have a series of checkpoints and steps that need to be properly regulated. TRIP13/PCH2 has been implicated in these processes in budding yeast as well, particularly in the meiosis G2/prophase stage. Double stranded breaks during meiosis is a key part of this phase and is impacted by TRIP13. The homologous recombination that occurs following these breaks requires a protein complex to influence and structure appropriate chromosomal pairing.
In a paper by San-Segundo et al., localization assays and induced mutations in PCH2 in budding yeast was shown to be required for the meiotic checkpoint to prevent chromosome segregation when the recombination or chromosome synapsis are defective. TRIP13, PCH2's analog, was also shown to be required for the formation of the synaptonemal complex – the complex that structures chromosomal pairings. Without TRIP13, meiocytes had pericentric synaptic forks, less number of crossovers, and altered distribution of chiasma (the contact point between homologous chromosomes. For this synaptonemal complex (SC) formation, meiotic HORMADS need to be removed. For example, PCH2 was found to be needed to remove Hop1 from chromosomes during SC formation. Other HORMADs, such as HORMAD1 and HORMAD2, are also depleted from the chromosomal pairs with the help of TRIP13 in mice cells. Research shows a robust and varied role for TRIP13/PCH2 to remove various proteins for SC formation, thus allowing meiosis to continue. Further mechanistic evidence is needed to clarify other proteins affected by TRIP13 in meiosis G2/Prophase, and elucidate the wide ability to affect a multitude of proteins.
# Role in spindle assembly complex
Like its role in meiosis, TRIP13/PCH2 is also implicated in mitosis, particularly in the metaphase-to-anaphase transition and the Spindle Assembly Checkpoint (SAC). Its function also has impacts on the Anaphase Promoting Complex (APC). To continue from metaphase to anaphase, the cell must ensure chromosomes are bioriented and properly structured in order for correct and error-free separation of sister chromatids. This process requires many proteins to ensure dynamic timing and consistent response. In order for progression, the APC must be activated, which upon activation degrade securing. The APC is activated by CDC20, a protein that is silenced by the mitotic checkpoint complex (MCC). Of interest in relation to TRIP13 is Mad2, which has two forms (open O-Mad2 and closed C-Mad2) (2). When kinetochores are unattached, O-Mad2 converts to C-Mad2, which is then able to latch to CDC20, and essentially sequester it preventing mitotic progression.
Progression requires the disassembly of the MCC, which is found to be mediated by p31-Comet. This is through to occur in part by structural mimicry, where p31-Comet is structurally similar to C-Mad2. However, this process requires ATP, which is where TRIP13/PCH2 comes into play. Evidence shows that TRIP13/PCH2 uses p31-Comet as an adaptor protein to convert C-Mad2 into O-Mad2. However, the connection between TRIP13/PCH2 and the SAC is more nuanced. Experiments in human HeLa and HCT116 cells show that neither p31-Comet nor TRIP13 was particularly required for unperturbed mitosis, and that depleting P31-Comet only slightly impaired Mad2 inactivation. Additionally, research shows that without TRIP13, Mad2 exists exclusively in the closed form. Interestingly, in TRIP13 deficient cells, the SAC was unable to be inactivated and had a relatively short mitosis. This hints at the possibility that activation of the SAC and the formation of the MCC requires not only C-Mad2 but also the conversion of C-Mad2 to O-Mad2.
# Implications in cancer
Given TRIP13/PCH2's role in the correct biorientation of chromosomes during mitosis, it is unsurprising that it is connected to several cancers. In one instance, overexpression of TRIP13 has been shown to affect treatment resistance for Squamous cell carcinoma of the head and neck. Additionally, TRIP13 and Mad2 overexpression are correlated jointly in cancer. In relation to mitotic delays associated with Mad2 overexpression, overexpression of TRIP13 reduced and TRIP13 reduction increased the mitotic delay that Mad2 overexpression brings about. Furthermore, Mad2 over-expression and TRIP13 decrease inhibited proliferation in cells and tumor xenografts – presenting therapeutic value for TRIP13 reduction. | TRIP13
TRIP13 is a mammalian gene that encodes the thyroid receptor-interacting protein 13. In budding yeast, the analog for TRIP13 is PCH2. TRIP13 is a member of the AAA+ ATPase family, a family known for mechanical forces derived from ATP hydrolase reactions. The TRIP13 gene has been shown to interact with a variety of proteins and implicated in a few diseases, notably interacting with the ligand binding domain of thyroid hormone receptors, and may play a role in early-stage non-small cell lung cancer.[1] However, recent evidence implicates TRIP13 in various cell cycle phases, including meiosis G2/Prophase and during the Spindle Assembly checkpoint (SAC). Evidence shows regulation to occur through the HORMA domains, including Hop1, Rev7, and Mad2.[2] Of note, Mad2's involvement in the SAC is shown to be affected by TRIP13 [3] Due to TRIP13's role in cell cycle arrest and progression, it may present opportunity as a therapeutic candidate for cancers.[4]
# Structure
As an AAA+ ATPase, TRIP13 (and its PCH2 analog) forms homohexamers and interacts with ATP as an energy source. With respect to Hop1, PCH2 binds to and structurally changes Hop1, displacing the Hop1 from DNA.[5] TRIP13/PCH2 interacts with ATP as a hydrolase, hydrolyzing phosphates to derive energy for conformational changes that can induce mechanical force on its substrate, Hop1 in the previous case.[6] TRIP14/PCH2 is believed to have a single AAA+ ATPase domain.[2] TRIP13/PCH2 also functions as a kinetochore protein that interacts with the silencing protein p31-Comet.[7]
# Role in meiosis G2/prophase
Meiosis in mammalian cells have a series of checkpoints and steps that need to be properly regulated. TRIP13/PCH2 has been implicated in these processes in budding yeast as well, particularly in the meiosis G2/prophase stage.[8] Double stranded breaks during meiosis is a key part of this phase and is impacted by TRIP13. The homologous recombination that occurs following these breaks requires a protein complex to influence and structure appropriate chromosomal pairing.
In a paper by San-Segundo et al., localization assays and induced mutations in PCH2 in budding yeast was shown to be required for the meiotic checkpoint to prevent chromosome segregation when the recombination or chromosome synapsis are defective.[8] TRIP13, PCH2's analog, was also shown to be required for the formation of the synaptonemal complex – the complex that structures chromosomal pairings. Without TRIP13, meiocytes had pericentric synaptic forks, less number of crossovers, and altered distribution of chiasma (the contact point between homologous chromosomes.[9] For this synaptonemal complex (SC) formation, meiotic HORMADS need to be removed. For example, PCH2 was found to be needed to remove Hop1 from chromosomes during SC formation.[10] Other HORMADs, such as HORMAD1 and HORMAD2, are also depleted from the chromosomal pairs with the help of TRIP13 in mice cells.[11] Research shows a robust and varied role for TRIP13/PCH2 to remove various proteins for SC formation, thus allowing meiosis to continue. Further mechanistic evidence is needed to clarify other proteins affected by TRIP13 in meiosis G2/Prophase, and elucidate the wide ability to affect a multitude of proteins.
# Role in spindle assembly complex
Like its role in meiosis, TRIP13/PCH2 is also implicated in mitosis, particularly in the metaphase-to-anaphase transition and the Spindle Assembly Checkpoint (SAC). Its function also has impacts on the Anaphase Promoting Complex (APC).[2] To continue from metaphase to anaphase, the cell must ensure chromosomes are bioriented and properly structured in order for correct and error-free separation of sister chromatids. This process requires many proteins to ensure dynamic timing and consistent response. In order for progression, the APC must be activated, which upon activation degrade securing. The APC is activated by CDC20, a protein that is silenced by the mitotic checkpoint complex (MCC). Of interest in relation to TRIP13 is Mad2, which has two forms (open O-Mad2 and closed C-Mad2)[2] (2). When kinetochores are unattached, O-Mad2 converts to C-Mad2, which is then able to latch to CDC20, and essentially sequester it preventing mitotic progression.[12]
Progression requires the disassembly of the MCC, which is found to be mediated by p31-Comet.[13] This is through to occur in part by structural mimicry, where p31-Comet is structurally similar to C-Mad2.[14] However, this process requires ATP, which is where TRIP13/PCH2 comes into play. Evidence shows that TRIP13/PCH2 uses p31-Comet as an adaptor protein to convert C-Mad2 into O-Mad2.[15] However, the connection between TRIP13/PCH2 and the SAC is more nuanced. Experiments in human HeLa and HCT116 cells show that neither p31-Comet nor TRIP13 was particularly required for unperturbed mitosis, and that depleting P31-Comet only slightly impaired Mad2 inactivation. Additionally, research shows that without TRIP13, Mad2 exists exclusively in the closed form. Interestingly, in TRIP13 deficient cells, the SAC was unable to be inactivated and had a relatively short mitosis. This hints at the possibility that activation of the SAC and the formation of the MCC requires not only C-Mad2 but also the conversion of C-Mad2 to O-Mad2.[16]
# Implications in cancer
Given TRIP13/PCH2's role in the correct biorientation of chromosomes during mitosis, it is unsurprising that it is connected to several cancers. In one instance, overexpression of TRIP13 has been shown to affect treatment resistance for Squamous cell carcinoma of the head and neck.[17] Additionally, TRIP13 and Mad2 overexpression are correlated jointly in cancer. In relation to mitotic delays associated with Mad2 overexpression, overexpression of TRIP13 reduced and TRIP13 reduction increased the mitotic delay that Mad2 overexpression brings about. Furthermore, Mad2 over-expression and TRIP13 decrease inhibited proliferation in cells and tumor xenografts – presenting therapeutic value for TRIP13 reduction.[18] | https://www.wikidoc.org/index.php/TRIP13 | |
eb6ab287e355053f0f0d994f5038d54c759ee9cf | wikidoc | TSG101 | TSG101
Tumor susceptibility gene 101, also known as TSG101, is a human gene that encodes for a cellular protein of the same name.
# Function
The protein encoded by this gene belongs to a group of apparently inactive homologs of ubiquitin-conjugating enzymes. The gene product contains a coiled-coil domain that interacts with stathmin, a cytosolic phosphoprotein implicated in tumorigenesis. The protein may play a role in cell growth and differentiation and act as a negative growth regulator. In vitro steady-state expression of this tumor susceptibility gene appears to be important for maintenance of genomic stability and cell cycle regulation. Mutations and alternative splicing in this gene occur in high frequency in breast cancer and suggest that defects occur during breast cancer tumorigenesis and/or progression.
The main role of ESCRT-I is to recognise ubiquitinated cargo via the UEV protein domain of the VPS23/TSG101 subunit. The assembly of the ESCRT-I complex is directed by the C-terminal steadiness box (SB) of VPS23, the N-terminal half of VPS28, and the C-terminal half of VPS37. The structure is primarily composed of three long, parallel helical hairpins, each corresponding to a different subunit. The additional domains and motifs extending beyond the core serve as gripping tools for ESCRT-I critical functions.
# HIV
TSG101 seems to play an important role in the pathogenesis of HIV. In uninfected cells, TSG101 functions in the biogenesis of the multivesicular body (MVB), which suggests that HIV may bind TSG101 in order to gain access to the downstream machinery that catalyzes MVB vesicle budding.
# Interactions
TSG101 has been shown to interact with:
- EP300,
- HGS,
- LRSAM1,
- P21,
- P53, and
- VPS28.
# Orthologue, Vps23
In humans, the orthologue of vps23 which has a component of ESCRT-1 is called Tsg101. Mutations in Tsg-101 have been linked to cervical, breast, prostate and gastrointestinal cancers. In molecular biology, vps23 (vacuolar protein sorting) is a protein domain. Vps proteins are components of the ESCRTs (endosomal sorting complexes required for transport) which are required for protein sorting at the early endosome. More specifically, vps23 is a component of ESCRT-I. The ESCRT complexes form the machinery driving protein sorting from endosomes to lysosomes. ESCRT complexes are central to receptor down-regulation, lysosome biogenesis and budding of HIV.
# Structure
Yeast ESCRT-I consists of three protein subunits, VPS23, VPS28, and VPS37. In humans, ESCRT-I comprises TSG101, VPS28, and one of four potential human VPS37 homologues. | TSG101
Tumor susceptibility gene 101, also known as TSG101, is a human gene that encodes for a cellular protein of the same name.
# Function
The protein encoded by this gene belongs to a group of apparently inactive homologs of ubiquitin-conjugating enzymes. The gene product contains a coiled-coil domain that interacts with stathmin, a cytosolic phosphoprotein implicated in tumorigenesis. The protein may play a role in cell growth and differentiation and act as a negative growth regulator. In vitro steady-state expression of this tumor susceptibility gene appears to be important for maintenance of genomic stability and cell cycle regulation. Mutations and alternative splicing in this gene occur in high frequency in breast cancer and suggest that defects occur during breast cancer tumorigenesis and/or progression.[1]
The main role of ESCRT-I is to recognise ubiquitinated cargo via the UEV protein domain of the VPS23/TSG101 subunit. The assembly of the ESCRT-I complex is directed by the C-terminal steadiness box (SB) of VPS23, the N-terminal half of VPS28, and the C-terminal half of VPS37. The structure is primarily composed of three long, parallel helical hairpins, each corresponding to a different subunit. The additional domains and motifs extending beyond the core serve as gripping tools for ESCRT-I critical functions.[2][3]
# HIV
TSG101 seems to play an important role in the pathogenesis of HIV. In uninfected cells, TSG101 functions in the biogenesis of the multivesicular body (MVB),[4] which suggests that HIV may bind TSG101 in order to gain access to the downstream machinery that catalyzes MVB vesicle budding.[5]
# Interactions
TSG101 has been shown to interact with:
- EP300,[6]
- HGS,[7][8]
- LRSAM1,[7][9]
- P21,[10]
- P53,[11] and
- VPS28.[7][12][13]
# Orthologue, Vps23
In humans, the orthologue of vps23 which has a component of ESCRT-1 is called Tsg101. Mutations in Tsg-101 have been linked to cervical, breast, prostate and gastrointestinal cancers. In molecular biology, vps23 (vacuolar protein sorting) is a protein domain. Vps proteins are components of the ESCRTs (endosomal sorting complexes required for transport) which are required for protein sorting at the early endosome. More specifically, vps23 is a component of ESCRT-I. The ESCRT complexes form the machinery driving protein sorting from endosomes to lysosomes. ESCRT complexes are central to receptor down-regulation, lysosome biogenesis and budding of HIV.
# Structure
Yeast ESCRT-I consists of three protein subunits, VPS23, VPS28, and VPS37. In humans, ESCRT-I comprises TSG101, VPS28, and one of four potential human VPS37 homologues. | https://www.wikidoc.org/index.php/TSG101 | |
7b6349561d6bc782b36942403eb5d5db355c5df6 | wikidoc | TSPAN4 | TSPAN4
Tetraspanin-4 is a protein that in humans is encoded by the TSPAN4 gene.
The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein and is similar in sequence to its family member CD53 antigen. It is known to complex with integrins and other transmembrane 4 superfamily proteins. Alternatively spliced transcript variants encoding different isoforms have been identified.
# Interactions
TSPAN4 has been shown to interact with CD9, ITGA6, CD29, CD49c and CD81. | TSPAN4
Tetraspanin-4 is a protein that in humans is encoded by the TSPAN4 gene.[1][2]
The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein and is similar in sequence to its family member CD53 antigen. It is known to complex with integrins and other transmembrane 4 superfamily proteins. Alternatively spliced transcript variants encoding different isoforms have been identified.[2]
# Interactions
TSPAN4 has been shown to interact with CD9,[1] ITGA6,[1] CD29,[1] CD49c[1] and CD81.[1] | https://www.wikidoc.org/index.php/TSPAN4 | |
ed490c1a75162584713c9fe91b0c559d21d39854 | wikidoc | TSPAN8 | TSPAN8
Tetraspanin-8 is a protein that in humans is encoded by the TSPAN8 gene.
# Function
The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein that is known to complex with integrins. This gene is expressed in different carcinomas. The use of alternate polyadenylation sites has been found for this gene.
# Clinical significance
Overall survival of breast cancer patients was effectively predicted by TSPAN8. | TSPAN8
Tetraspanin-8 is a protein that in humans is encoded by the TSPAN8 gene.[1][2]
# Function
The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein that is known to complex with integrins. This gene is expressed in different carcinomas. The use of alternate polyadenylation sites has been found for this gene.[2]
# Clinical significance
Overall survival of breast cancer patients was effectively predicted by TSPAN8.[3] | https://www.wikidoc.org/index.php/TSPAN8 | |
a69222679690c6dc3e456ff7d9d60373a08f2662 | wikidoc | TUBA1A | TUBA1A
Tubulin alpha-1A chain is a protein that in humans is encoded by the TUBA1A gene.
# Background
TUBA1A is a structural gene that encodes for Tubulin, Alpha 1A product. TUBA1A product is an alpha-tubulin that participates in the formation of microtubules - structural proteins that participate in cytoskeletal structure. Specifically, microtubules are composed of a heterodimer of alpha and beta-tubulin molecules. Cowan et al. demonstrated that bα1 is a primary α-tubulin of the human fetal brain, and that it is expressed solely in that structure, by way of Northern blot. Miller et al. further elaborated on the role of α-tubulins and the process of neuronal development and maturation, comparing the expressions of rat α-tubulins Tα1 and T26. These two rat α-tubulins are homologs of bα1 and kα1 showing that a rat homolog of human TUBA1A (Tα1) had elevated expression during the extension of neuronal processes. Culturing of pheochromocytoma cells with Nerve Growth Factor (NGF) induced differentiation and the development of neuronal processes. Northern blot assay showed markedly elevated levels of Tα1 mRNA expression; T26 mRNA expression increased minimally with exposure to NGF. These data suggest that TUBA1A models the brain by participating in the directing of neuronal migration through the ability of microtubules to readily form and break polymers to extend and retract processes to induce nucleokinesis. Poirier et al. used RNA in situ hybridization to show TUBA1A expression in mice embryo; embryo sections from embryonic day 16.5 “showed a strong labeling in the telencephalon, diencephalon, and mesencephalon, the developing cerebellum, the brainstem, the spinal cord, and the dorsal root ganglia”.
# Function
Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulins. The genes encoding these microtubule constituents belong to the tubulin superfamily, which is composed of six distinct families. Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent the major components of microtubules, while gamma tubulin plays a critical role in the nucleation of microtubule assembly. There are multiple alpha and beta tubulin genes, which are highly conserved among species. This gene encodes alpha tubulin and is highly similar to mouse and rat Tuba1 gene. Northern blotting studies have shown that the gene expression is predominantly found in morphologically differentiated neurologic cells. This gene is one of three alpha-tubulin genes in a cluster on chromosome 12q.
# Interactions
TUBA1A has been shown to interact with PAFAH1B1.
# Disease
Mutations to the TUBA1A gene manifest clinically as Type 3 Lissencephaly. In general, lissencephaly is characterized by agyria (lacking of gyri and sulci to the brain – a smooth brain), seizure activity, failure to thrive, as well as intellectual disability and psychomotor retardation, often to a profound degree.
The symptoms of Lis3 Lissencephaly are not especially different from generalized lissencephaly (Lis1, related to PAFAH1B1). Diagnosis of lissencephaly generally is made from the symptom profile, while attribution to a specific type is obtained by microarray. Treatment is symptomatic; anti-convulsive drugs for seizure activity, g-button gastrostomy to feed the child, physical therapy for muscle disorders. TUBA1A mutation is common in microlissencephaly
# Animal Model
Keays et al. describe a mouse with a mutation of the TUBA1A gene induced by N-ethyl-N-nitrosourea. The relevant point mutation resulted in S140G; the site of the mutation participates in the N-site of the formed α-tubulin, and participates in stabilizing the α-β tubulin polymer by binding GTP at this site. The S140G mutation resulted in the formation of a “compromised GTP binding pocket”. Authors note defects associated with cortical layers II/III and IV, especially in cortical neuronal migration (with respect to wild-type counterparts), showing that the S140G mutation has value as a model for detailing disease associated with the Human TUBA homolog. | TUBA1A
Tubulin alpha-1A chain is a protein that in humans is encoded by the TUBA1A gene.[1][2][3]
# Background
TUBA1A is a structural gene that encodes for Tubulin, Alpha 1A product. TUBA1A product is an alpha-tubulin that participates in the formation of microtubules - structural proteins that participate in cytoskeletal structure. Specifically, microtubules are composed of a heterodimer of alpha and beta-tubulin molecules. Cowan et al. demonstrated that bα1 is a primary α-tubulin of the human fetal brain, and that it is expressed solely in that structure, by way of Northern blot.[4] Miller et al. further elaborated on the role of α-tubulins and the process of neuronal development and maturation, comparing the expressions of rat α-tubulins Tα1 and T26. These two rat α-tubulins are homologs of bα1 and kα1 showing that a rat homolog of human TUBA1A (Tα1) had elevated expression during the extension of neuronal processes. Culturing of pheochromocytoma cells with Nerve Growth Factor (NGF) induced differentiation and the development of neuronal processes. Northern blot assay showed markedly elevated levels of Tα1 mRNA expression; T26 mRNA expression increased minimally with exposure to NGF.[5] These data suggest that TUBA1A models the brain by participating in the directing of neuronal migration through the ability of microtubules to readily form and break polymers to extend and retract processes to induce nucleokinesis.[6] Poirier et al. used RNA in situ hybridization to show TUBA1A expression in mice embryo; embryo sections from embryonic day 16.5 “showed a strong labeling in the telencephalon, diencephalon, and mesencephalon, the developing cerebellum, the brainstem, the spinal cord, and the dorsal root ganglia”.[7]
# Function
Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulins. The genes encoding these microtubule constituents belong to the tubulin superfamily, which is composed of six distinct families. Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent the major components of microtubules, while gamma tubulin plays a critical role in the nucleation of microtubule assembly. There are multiple alpha and beta tubulin genes, which are highly conserved among species. This gene encodes alpha tubulin and is highly similar to mouse and rat Tuba1 gene. Northern blotting studies have shown that the gene expression is predominantly found in morphologically differentiated neurologic cells. This gene is one of three alpha-tubulin genes in a cluster on chromosome 12q.[3]
# Interactions
TUBA1A has been shown to interact with PAFAH1B1.[8]
# Disease
Mutations to the TUBA1A gene manifest clinically as Type 3 Lissencephaly. In general, lissencephaly is characterized by agyria (lacking of gyri and sulci to the brain – a smooth brain), seizure activity, failure to thrive, as well as intellectual disability and psychomotor retardation, often to a profound degree.[7]
The symptoms of Lis3 Lissencephaly are not especially different from generalized lissencephaly (Lis1, related to PAFAH1B1). Diagnosis of lissencephaly generally is made from the symptom profile, while attribution to a specific type is obtained by microarray. Treatment is symptomatic; anti-convulsive drugs for seizure activity, g-button gastrostomy to feed the child, physical therapy for muscle disorders. TUBA1A mutation is common in microlissencephaly
# Animal Model
Keays et al. describe a mouse with a mutation of the TUBA1A gene induced by N-ethyl-N-nitrosourea. The relevant point mutation resulted in S140G;[9] the site of the mutation participates in the N-site of the formed α-tubulin, and participates in stabilizing the α-β tubulin polymer by binding GTP at this site.[10] The S140G mutation resulted in the formation of a “compromised GTP binding pocket”. Authors note defects associated with cortical layers II/III and IV, especially in cortical neuronal migration (with respect to wild-type counterparts), showing that the S140G mutation has value as a model for detailing disease associated with the Human TUBA homolog.[9] | https://www.wikidoc.org/index.php/TUBA1A | |
47190ad0e221ae70b667766aeb635a01318abf19 | wikidoc | TUC338 | TUC338
TUC338 (transcribed ultra-conserved region 338) is an ultra-conserved element which is transcribed to give a non-coding RNA. The TUC338 gene was first identified as uc.338, along with 480 other ultra-conserved elements in the human genome. Expression of this RNA gene has been found to dramatically increase in hepatocellular carcinoma (HCC) cells.
The TUC338 RNA gene is 590 base-pairs long, and partially overlaps the gene encoding Poly(rC)-binding protein 2 (PCBP2), a protein involved in mRNA processing. Despite this overlap, PCBP2 and TUC388 were found to be independently expressed.
TUC338 is predicted to function in cell growth, possibly at the interface between G1 phase and S phase, and could potentially present a therapeutic target to treat HCC cells. Experimental evidence shows knocking out TUC338 using siRNA reduced the growth rate of both mouse and human HCC cells. | TUC338
TUC338 (transcribed ultra-conserved region 338) is an ultra-conserved element which is transcribed to give a non-coding RNA.[1][2] The TUC338 gene was first identified as uc.338, along with 480 other ultra-conserved elements in the human genome.[3] Expression of this RNA gene has been found to dramatically increase in hepatocellular carcinoma (HCC) cells.[4]
The TUC338 RNA gene is 590 base-pairs long, and partially overlaps the gene encoding Poly(rC)-binding protein 2 (PCBP2), a protein involved in mRNA processing.[5] Despite this overlap, PCBP2 and TUC388 were found to be independently expressed.[4]
TUC338 is predicted to function in cell growth, possibly at the interface between G1 phase and S phase, and could potentially present a therapeutic target to treat HCC cells.[4] Experimental evidence shows knocking out TUC338 using siRNA reduced the growth rate of both mouse and human HCC cells.[4] | https://www.wikidoc.org/index.php/TUC338 | |
ae788866da4309863dcdc433a3fb999ef0402589 | wikidoc | Tables | Tables
# Overview
This page gives information about syntax to build wiki-tables in MediaWiki.
- Tables (Youtube)
# Customizing the Column Widths
## Output
- The wiki markup will generate a table as follows:
# Using the Toolbar
You can use the Mediawiki edit toolbar to create tables.The toolbar is helpful to generate the necessary codings.
Use the first button on the right of the toolbar to insert a table when editing a page.
By default, it includes the next text:
{| class="wikitable"
! header 1
! header 2
! header 3
# Pipe syntax tutorial
Although HTML table syntax also works, special wikicode can be used as a shortcut to create a table. The pipe (vertical bar) codes function exactly the same as HTML table markup, so a knowledge of HTML table code will help in understanding pipe code. The shortcuts are as follows:
- The entire table is encased with curly brackets and a vertical bar character (a pipe). So use {| to begin a table, and |} to end it. Each one needs to be on its own line:
- An optional table caption is included with a line starting with a vertical bar and plus sign "|+" and the caption after it:
- To start a new table row, type a vertical bar and a hyphen on its own line: "|-". The codes for the cells in that row will start on the next line.
- Type the codes for each table cell in the next row, starting with a bar:
- Cells can be separated with either a new line and new bar, or by a double bar "||" on the same line. Both produce the same output:
- If you use single bars, then what you think the first cell is in fact a format modifier applied to the cell, and the the rest of your "cells" are merged into one:
which is probably not what you want:
However, the format modifier is useful:
Just remember: no more than 2 single pipes on a line!
- a row of column headings is identified by using "!" instead of "|", and using "!!" instead of "||". Header cells typically render differently than regular cells, depending on the browser. They are often rendered in a bold font and centered.
- the first cell of a row is identified as row heading by starting the line with "!" instead of "|", and starting subsequent data cells on a new line.
- Optional parameters can modify the behavior of cells, rows, or the entire table. For instance, a border could be added to the table:
The final table would display like this:
The table parameters and cell parameters are the same as in HTML, see and Table (HTML). However, the thead, tbody, tfoot, colgroup, and col elements are currently not supported in MediaWiki.
A table can be useful even if none of the cells have content. For example, the background colors of cells can be changed with cell parameters, making the table into a diagram, like m:Template talk:Square 8x8 pentomino example. An "image" in the form of a table is much more convenient to edit than an uploaded image.
Each row must have the same number of cells as the other rows, so that the number of columns in the table remains consistent (unless there are cells which span several columns or rows, see colspan and rowspan in Mélange example below). For empty cells, use the non-breaking space as content to ensure that the cells are displayed. To show a visible pipe in a cell, use | or |.
# Examples
## Simple example
Both of these generate the same output. Choose a style based on the number of cells in each row and the total text inside each cell.
Wiki markup
What it looks like in your browser
## Multiplication table
Wiki markup
What it looks like in your browser (see: Help:User_style)
## Color; scope of parameters
Two ways of specifying color of text and background for a single cell are as follows. The first form is preferred:
Wiki markup
What it looks like in your browser
Like other parameters, colors can also be specified for a whole row or the whole table; parameters for a row override the value for the table, and those for a cell override those for a row:
Wiki markup
What it looks like in your browser
To make the table blend in with the background, use style="background:none". (Warning: style="background:inherit", does not work with some browsers, including IE6!)
## Width, height
The width and height of the whole table can be specified, as well as the height of a row. To specify the width of a column one can specify the width of an arbitrary cell in it. If the width is not specified for all columns, and/or the height is not specified for all rows, then there is some ambiguity, and the result depends on the browser.
Wiki markup
What it looks like in your browser
Note that style="inline CSS" has no effect with some browsers. If compatibility is important, equivalent older constructs like width="75%" should work on more browsers.
### Setting your column widths
If you wish to force column widths to your own requirements, rather than accepting the width of the widest text element in a column's cells, then follow this example. Note that wrap-around of text is forced.
To set column widths in a table without headers, specify the width in the first cell for each column, like this:
## Vertical alignment
By default data in tables is vertically centrally aligned, which results in odd-looking layouts like this:
To fix this, apply the valign="top" attribute to the rows (unfortunately it seems to be necessary to apply this individually to every single row). For example:
## Positioning
One can position the table itself, and all contents in a row, and contents in a cell, but not with a single parameter for all contents in the table, see m:Template talk:Table demo. Do not, under any circumstances, use "float" to position a table. It will break page rendering at large font sizes.
## Mélange
Here's a more advanced example, showing some more options available for making up tables. You can play with these settings in your own table to see what effect they have. Not all of these techniques may be appropriate in all cases; just because you can add colored backgrounds, for example, doesn't mean it's always a good idea. Try to keep the markup in your tables relatively simple -- remember, other people are going to be editing the article too! This example should give you an idea of what is possible, though.
Wiki markup
What it looks like in your browser
## Floating table
Wiki markup
What it looks like in your browser
This paragraph is before the table. Lorem ipsum dolor sit
amet, consectetur adipisicing elit, sed do eiusmod tempor
incididunt ut labore et dolore magna aliqua. Ut enim ad
minim veniam, quis nostrud exercitation...
Note the floating table to the right.
This paragraph is after the table. Lorem ipsum dolor sit
amet, consectetur adipisicing elit, sed do eiusmod tempor
incididunt ut labore et dolore magna aliqua. Ut enim ad
minim veniam, quis nostrud exercitation...
## Nested tables
This shows one table (in blue) nested inside another table's cell2. Nested tables have to start on a new line.
Wiki markup
{| border="1"
{| border="2" style="background-color:#ABCDEF;"
What it looks like in your browser
## Combined use of COLSPAN and ROWSPAN
Wiki markup
What it looks like in your browser
Note that using rowspan="2" for cell G combined with rowspan="3" for cell F to get another row below G and F won't work, because all (implicit) cells would be empty.
Likewise complete columns are not displayed if all their cells are empty. Borders between non-empty and empty cells might be also not displayed (depending on the browser), use to fill an empty cell with dummy content.
## Centering tables
Centered tables can be achieved, but they will not "float"; that is to say, no text will appear to either side. The trick is {| style="margin: 1em auto 1em auto"
Wiki markup
What it looks like in your browser
## Setting parameters
At the start of a cell, add your parameter followed by a single pipe. For example width="300"| will set that cell to a width of 300 pixels. To set more than one parameter, leave a space between each one.
Wiki markup
What it looks like in your browser
## Decimal point alignment
A method to get columns of numbers aligned at the decimal point is as follows:
Wiki markup
What it looks like in your browser
If the column of numbers appears in a table with cell padding or cell spacing, one can still align the decimal points without an unsightly gap in the middle. Embed a table in each number's cell and specify its column widths. Make the embedded tables' column widths the same for each cell in the column. (If decimal points are still misaligned using this method, the main table's column may be too narrow. Add a parameter to increase the column's width.)
Wiki markup
What it looks like in your browser
In simple cases one can dispense with the table feature and simply start the lines with a space, and put spaces to position the numbers:
# Style classes
Some users have created CSS classes and templates to make table styles easier. Instead of remembering table parameters, you just include an appropriate style class after the {|. This helps keep table formatting consistent, and can allow a single change to the class to fix a problem or enhance the look of all the tables that are using it at once. For instance, this:
simply by replacing inline CSS for the table by class="wikitable". This is because the wikitable class in MediaWiki:Common.css contains a number of table.wikitable CSS style rules. These are all applied at once when you mark a table with the class. You can then add additional style rules if desired. These override the class's rules, allowing you to use the class style as a base and build up on it:
Wiki markup
What it looks like in your browser
Notice that the table retains the gray background of the wikitable class, and the headers are still bold and centered. But now the text formatting has been overridden by the local style statement; all of the text in the table has been made italic and 120% normal size, and the wikitable border has been replaced by the red dashed border.
Of course this works only for browsers supporting inline CSS, if it's important use XHTML markup like instead of "font-size:120%", or Wiki markup like ''text'' instead of "font-style:italic".
# Sorting
For a sortable table (wikitable sortable) see Help:Sorting.
# Table row depending on a template parameter
Wiki-syntax for a table row can be made optional using ParserFunctions. To avoid confusion between pipe characters as used in ParserFunctions, and those which are part of the table syntax, the latter are put with a special Template:Tim, see Template:Tim.
# Other table syntax
Other types of table syntax that MediaWiki supports:
- XHTML
- HTML and wiki syntax (Do not use)
All three are supported by MediaWiki and create (currently) valid HTML output, but the pipe syntax is the simplest, especially for people who are already familiar with HTML. Also, HTML and wiki syntax will not necessarily remain browser-supported in the upcoming future, especially on handheld internet-accessible devices.
See also Table (HTML), HTML element#Tables. Note however that the thead, tbody, tfoot, colgroup, and col elements are currently not supported in MediaWiki.
## Comparison of table syntax
# Pipe syntax in terms of the HTML produced
The pipe syntax, developed by Magnus Manske, substitutes pipes (|) for HTML. There is an on-line script which converts html tables to pipe syntax tables.
The pipes must start at the beginning of a new line, except when separating parameters from content or when using || to separate cells on a single line. The parameters are optional.
## Tables
A table is defined by
{| ''params''
which equals
Insert non-formatted text here
## Rows
tags will be generated automatically for the first row. To start a new row, use
which results in
Parameters can be added like this:
which results in
Note:
- tags will be automatically opened at the first equivalent
- tags will be automatically closed at and equivalents
## Cells
Cells are generated either like this:
-r like this:
which both equal
so "||" equals "newline" + "|"
Parameters in cells can be used like this:
which will result in
## Headers
Functions the same way as TD, except "!" is used instead of the opening "|". "!!" can be used instead of "||". Parameters still use "|", though! Example:
## Captions
A tag is created by
which generates
You can also use parameters:
which will generate
# Displaying the table code which generates a table
A simple wiki markup table's code inside a Code box can be seen below.
Above code produces/displays below table:
Below code, generated and displayed the above table's Code box code itself, on the screen and web page, inside a blue colored dashed bordered rectangular box.
Note that, HTML tag was used to achieve displaying the above code and the Code box.
## Other alternatives to display table code
In most cases, when a code line is longer than the web browser window's width, then a scrolling bar appears at bottom, to let the viewer slide to the right side (and also left side) to see the rest of the code, because, the use of tag causes code lines to remain intact, unless an EOL (CR/LF) hidden character is reached in that text line. But having to slide or scroll to the right or left to view the full code line is often not comfortable to many users. To solve such problem, using the , and HTML tags, are better than using the tag, as those will not result in the need to move the scroll-bar to the right (or left) side for viewing, by causing code lines to wrap around so that they don't exceed the length allowed by the web browser window's width. By placing the code inside the ... HTML tags, the code is displayed with a fixed width text/font, (like the tag uses) for easier reading. HTML tag is used to display (or bring) next line of code, starting from the next line. HTML tag along with its CSS style properties, is used to create the blue colored dashed bordered rectangular box (Code box) around the codes, (like the HTML tag, which gets these properties from the main.css stylesheet file).
An example of table code with a long line is:
{| border="5" cellspacing="5" cellpadding="2"
! Computer
producing the below table:
The Code box above the table has the auto line wrapping feature enabled. Note the long line of code (the sixth line from top), which is wrapped inside the Code box. This Code box and the code inside it, can be displayed by using the below code in the edit box.
{| border="5" cellspacing="5" cellpadding="2"
! Computer
See the above codes, note that, ... tags were used to disable wiki markup codes for beginning a table ({|), ending a table (|}), start of an image displaying ([[), or a hyperlink, etc. All wiki & HTML markup codes need to be disabled by enclosing them inside the ... tags. If these codes were to be displayed inside another table, then, each | (pipe) & ! (Exclamation mark) symbol also needed to be enclosed inside the tags. Note that, the longer line is automatically wrapped according to the width of the web browser's window, inside the Code box.
Alternatively, we can replace each | (pipe symbol) character with | (HTML decimal entity code), replace each ! (exclamation mark) with ! code, replace { (beginning curly/second bracket) with { and we may replace } (closing curly/second bracket) with } code. Also replace the < (less than sign, or beginning angle bracket) with < numeric entity code or, replace it with < (HTML symbol entity code). For more on HTML decimal or hexadecimal numeric entity codes, please see w:Windows Alt codes. To display the wiki image markup code, we should replace the (closing square/third bracket) with ]. When we are replacing characters with their numeric enitity codes, we are actually disabling their normal functionality, so we can display them on the web page(s).
{| border="5" cellspacing="5" cellpadding="2"
| style="text-align: center;" | [[Image:gnome-system.png]]
! Computer
| style="color: yellow; background-color: green;" | Processor Speed: <span style="color: red;"> 1.8 GHz </span> | Tables
# Overview
This page gives information about syntax to build wiki-tables in MediaWiki.
- Tables (Youtube)
# Customizing the Column Widths
## Output
- The wiki markup will generate a table as follows:
# Using the Toolbar
You can use the Mediawiki edit toolbar to create tables.The toolbar is helpful to generate the necessary codings.
Use the first button on the right of the toolbar to insert a table when editing a page.
By default, it includes the next text:
{| class="wikitable"
! header 1
! header 2
! header 3
# Pipe syntax tutorial
Although HTML table syntax also works, special wikicode can be used as a shortcut to create a table. The pipe (vertical bar) codes function exactly the same as HTML table markup, so a knowledge of HTML table code will help in understanding pipe code. The shortcuts are as follows:
- The entire table is encased with curly brackets and a vertical bar character (a pipe). So use {| to begin a table, and |} to end it. Each one needs to be on its own line:
- An optional table caption is included with a line starting with a vertical bar and plus sign "|+" and the caption after it:
- To start a new table row, type a vertical bar and a hyphen on its own line: "|-". The codes for the cells in that row will start on the next line.
- Type the codes for each table cell in the next row, starting with a bar:
- Cells can be separated with either a new line and new bar, or by a double bar "||" on the same line. Both produce the same output:
- If you use single bars, then what you think the first cell is in fact a format modifier applied to the cell, and the the rest of your "cells" are merged into one:
which is probably not what you want:
However, the format modifier is useful:
Just remember: no more than 2 single pipes on a line!
- a row of column headings is identified by using "!" instead of "|", and using "!!" instead of "||". Header cells typically render differently than regular cells, depending on the browser. They are often rendered in a bold font and centered.
- the first cell of a row is identified as row heading by starting the line with "!" instead of "|", and starting subsequent data cells on a new line.
- Optional parameters can modify the behavior of cells, rows, or the entire table. For instance, a border could be added to the table:
The final table would display like this:
The table parameters and cell parameters are the same as in HTML, see [1] and Table (HTML). However, the thead, tbody, tfoot, colgroup, and col elements are currently not supported in MediaWiki.
A table can be useful even if none of the cells have content. For example, the background colors of cells can be changed with cell parameters, making the table into a diagram, like m:Template talk:Square 8x8 pentomino example. An "image" in the form of a table is much more convenient to edit than an uploaded image.
Each row must have the same number of cells as the other rows, so that the number of columns in the table remains consistent (unless there are cells which span several columns or rows, see colspan and rowspan in Mélange example below). For empty cells, use the non-breaking space as content to ensure that the cells are displayed. To show a visible pipe in a cell, use <nowiki>|</nowiki> or |.
# Examples
## Simple example
Both of these generate the same output. Choose a style based on the number of cells in each row and the total text inside each cell.
Wiki markup
What it looks like in your browser
## Multiplication table
Wiki markup
What it looks like in your browser (see: Help:User_style)
## Color; scope of parameters
Two ways of specifying color of text and background for a single cell are as follows. The first form is preferred:
Wiki markup
What it looks like in your browser
Like other parameters, colors can also be specified for a whole row or the whole table; parameters for a row override the value for the table, and those for a cell override those for a row:
Wiki markup
What it looks like in your browser
To make the table blend in with the background, use style="background:none". (Warning: style="background:inherit", does not work with some browsers, including IE6!)
## Width, height
The width and height of the whole table can be specified, as well as the height of a row. To specify the width of a column one can specify the width of an arbitrary cell in it. If the width is not specified for all columns, and/or the height is not specified for all rows, then there is some ambiguity, and the result depends on the browser.
Wiki markup
What it looks like in your browser
Note that style="inline CSS" has no effect with some browsers. If compatibility is important, equivalent older constructs like width="75%" should work on more browsers.
### Setting your column widths
If you wish to force column widths to your own requirements, rather than accepting the width of the widest text element in a column's cells, then follow this example. Note that wrap-around of text is forced.
To set column widths in a table without headers, specify the width in the first cell for each column, like this:
## Vertical alignment
By default data in tables is vertically centrally aligned, which results in odd-looking layouts like this:
To fix this, apply the valign="top" attribute to the rows (unfortunately it seems to be necessary to apply this individually to every single row). For example:
## Positioning
One can position the table itself, and all contents in a row, and contents in a cell, but not with a single parameter for all contents in the table, see m:Template talk:Table demo. Do not, under any circumstances, use "float" to position a table. It will break page rendering at large font sizes.
## Mélange
Here's a more advanced example, showing some more options available for making up tables. You can play with these settings in your own table to see what effect they have. Not all of these techniques may be appropriate in all cases; just because you can add colored backgrounds, for example, doesn't mean it's always a good idea. Try to keep the markup in your tables relatively simple -- remember, other people are going to be editing the article too! This example should give you an idea of what is possible, though.
Wiki markup
What it looks like in your browser
## Floating table
Wiki markup
What it looks like in your browser
This paragraph is before the table. Lorem ipsum dolor sit
amet, consectetur adipisicing elit, sed do eiusmod tempor
incididunt ut labore et dolore magna aliqua. Ut enim ad
minim veniam, quis nostrud exercitation...
Note the floating table to the right.
This paragraph is after the table. Lorem ipsum dolor sit
amet, consectetur adipisicing elit, sed do eiusmod tempor
incididunt ut labore et dolore magna aliqua. Ut enim ad
minim veniam, quis nostrud exercitation...
## Nested tables
This shows one table (in blue) nested inside another table's cell2. Nested tables have to start on a new line.
Wiki markup
{| border="1"
{| border="2" style="background-color:#ABCDEF;"
What it looks like in your browser
## Combined use of COLSPAN and ROWSPAN
Wiki markup
What it looks like in your browser
Note that using rowspan="2" for cell G combined with rowspan="3" for cell F to get another row below G and F won't work, because all (implicit) cells would be empty.
Likewise complete columns are not displayed if all their cells are empty. Borders between non-empty and empty cells might be also not displayed (depending on the browser), use to fill an empty cell with dummy content.
## Centering tables
Centered tables can be achieved, but they will not "float"; that is to say, no text will appear to either side. The trick is {| style="margin: 1em auto 1em auto"
Wiki markup
What it looks like in your browser
## Setting parameters
At the start of a cell, add your parameter followed by a single pipe. For example width="300"| will set that cell to a width of 300 pixels. To set more than one parameter, leave a space between each one.
Wiki markup
What it looks like in your browser
## Decimal point alignment
A method to get columns of numbers aligned at the decimal point is as follows:
Wiki markup
What it looks like in your browser
If the column of numbers appears in a table with cell padding or cell spacing, one can still align the decimal points without an unsightly gap in the middle. Embed a table in each number's cell and specify its column widths. Make the embedded tables' column widths the same for each cell in the column. (If decimal points are still misaligned using this method, the main table's column may be too narrow. Add a parameter to increase the column's width.)
Wiki markup
What it looks like in your browser
In simple cases one can dispense with the table feature and simply start the lines with a space, and put spaces to position the numbers:
# Style classes
Some users have created CSS classes and templates to make table styles easier. Instead of remembering table parameters, you just include an appropriate style class after the {|. This helps keep table formatting consistent, and can allow a single change to the class to fix a problem or enhance the look of all the tables that are using it at once. For instance, this:
simply by replacing inline CSS for the table by class="wikitable". This is because the wikitable class in MediaWiki:Common.css contains a number of table.wikitable CSS style rules. These are all applied at once when you mark a table with the class. You can then add additional style rules if desired. These override the class's rules, allowing you to use the class style as a base and build up on it:
Wiki markup
What it looks like in your browser
Notice that the table retains the gray background of the wikitable class, and the headers are still bold and centered. But now the text formatting has been overridden by the local style statement; all of the text in the table has been made italic and 120% normal size, and the wikitable border has been replaced by the red dashed border.
Of course this works only for browsers supporting inline CSS, if it's important use XHTML markup like <big> instead of "font-size:120%", or Wiki markup like ''text'' instead of "font-style:italic".
# Sorting
For a sortable table (wikitable sortable) see Help:Sorting.
# Table row depending on a template parameter
Wiki-syntax for a table row can be made optional using ParserFunctions. To avoid confusion between pipe characters as used in ParserFunctions, and those which are part of the table syntax, the latter are put with a special Template:Tim, see Template:Tim.
# Other table syntax
Other types of table syntax that MediaWiki supports:
- XHTML
- HTML and wiki <td> syntax (Do not use)
All three are supported by MediaWiki and create (currently) valid HTML output, but the pipe syntax is the simplest, especially for people who are already familiar with HTML. Also, HTML and wiki <td> syntax will not necessarily remain browser-supported in the upcoming future, especially on handheld internet-accessible devices.
See also Table (HTML), HTML element#Tables. Note however that the thead, tbody, tfoot, colgroup, and col elements are currently not supported in MediaWiki.
## Comparison of table syntax
# Pipe syntax in terms of the HTML produced
The pipe syntax, developed by Magnus Manske, substitutes pipes (|) for HTML. There is an on-line script which converts html tables to pipe syntax tables.
The pipes must start at the beginning of a new line, except when separating parameters from content or when using || to separate cells on a single line. The parameters are optional.
## Tables
A table is defined by
{| ''params''
|}
which equals
<table ''params''>Insert non-formatted text here
</table>
## Rows
<tr> tags will be generated automatically for the first row. To start a new row, use
which results in
Parameters can be added like this:
which results in
Note:
- <tr> tags will be automatically opened at the first <td> equivalent
- <tr> tags will be automatically closed at <tr> and </table> equivalents
## Cells
Cells are generated either like this:
or like this:
which both equal
so "||" equals "newline" + "|"
Parameters in cells can be used like this:
which will result in
## Headers
Functions the same way as TD, except "!" is used instead of the opening "|". "!!" can be used instead of "||". Parameters still use "|", though! Example:
## Captions
A <caption> tag is created by
which generates
You can also use parameters:
which will generate
# Displaying the table code which generates a table
A simple wiki markup table's code inside a Code box can be seen below.
Above code produces/displays below table:
Below code, generated and displayed the above table's Code box code itself, on the screen and web page, inside a blue colored dashed bordered rectangular box.
Note that, HTML tag <pre> was used to achieve displaying the above code and the Code box.
## Other alternatives to display table code
In most cases, when a code line is longer than the web browser window's width, then a scrolling bar appears at bottom, to let the viewer slide to the right side (and also left side) to see the rest of the code, because, the use of <pre> tag causes code lines to remain intact, unless an EOL (CR/LF) hidden character is reached in that text line. But having to slide or scroll to the right or left to view the full code line is often not comfortable to many users. To solve such problem, using the <p>, <tt> and <br /> HTML tags, are better than using the <pre> tag, as those will not result in the need to move the scroll-bar to the right (or left) side for viewing, by causing code lines to wrap around so that they don't exceed the length allowed by the web browser window's width. By placing the code inside the <tt>...</tt> HTML tags, the code is displayed with a fixed width text/font, (like the <pre> tag uses) for easier reading. HTML tag <br /> is used to display (or bring) next line of code, starting from the next line. HTML tag <p> along with its CSS style properties, is used to create the blue colored dashed bordered rectangular box (Code box) around the codes, (like the HTML <pre> tag, which gets these properties from the main.css stylesheet file).
An example of table code with a long line is:
{| border="5" cellspacing="5" cellpadding="2"
! Computer
producing the below table:
The Code box above the table has the auto line wrapping feature enabled. Note the long line of code (the sixth line from top), which is wrapped inside the Code box. This Code box and the code inside it, can be displayed by using the below code in the edit box.
<p style="padding: 1em; border: 1px dashed #2f6fab; color: Black; background-color: #f9f9f9; line-height: 1.1em;"> <tt>
<nowiki>{|</nowiki> border="5" cellspacing="5" cellpadding="2" <br />
! Computer <br />
<nowiki>|}</nowiki> <br />
</tt> </p>
See the above codes, note that, <nowiki>...</nowiki> tags were used to disable wiki markup codes for beginning a table ({|), ending a table (|}), start of an image displaying ([[), or a hyperlink, etc. All wiki & HTML markup codes need to be disabled by enclosing them inside the <nowiki>...</nowiki> tags. If these codes were to be displayed inside another table, then, each | (pipe) & ! (Exclamation mark) symbol also needed to be enclosed inside the <nowiki> tags. Note that, the longer line is automatically wrapped according to the width of the web browser's window, inside the Code box.
Alternatively, we can replace each | (pipe symbol) character with | (HTML decimal entity code), replace each ! (exclamation mark) with ! code, replace { (beginning curly/second bracket) with { and we may replace } (closing curly/second bracket) with } code. Also replace the < (less than sign, or beginning angle bracket) with < numeric entity code or, replace it with < (HTML symbol entity code). For more on HTML decimal or hexadecimal numeric entity codes, please see w:Windows Alt codes. To display the wiki image markup code, we should replace the [ (beginning square/third bracket) with [ and we may replace ] (closing square/third bracket) with ]. When we are replacing characters with their numeric enitity codes, we are actually disabling their normal functionality, so we can display them on the web page(s).
<p style="padding: 1em; border: 1px dashed #2f6fab; color: Black; background-color: #f9f9f9; line-height: 1.1em;"> <tt>
{| border="5" cellspacing="5" cellpadding="2" <br />
| style="text-align: center;" | [[Image:gnome-system.png]] <br />
|- <br />
! Computer <br />
|- <br />
| style="color: yellow; background-color: green;" | Processor Speed: <span style="color: red;"> 1.8 GHz </span> <br />
|} <br />
</tt> </p>
# External links
- HTML tables to wiki converter at cnic.org
- csv2wp - converts comma-separated values (CSV) format to pipe syntax. You may use this to import tables from Excel etc. (more information)
- HTML tables to wiki converter at uni-bonn.de
- HTML tables to wiki converter at diberri.dyndns.org
- pywikipediabot (can convert HTML tables to wiki)
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Tables | |
710614128a13d5f081697edd689eabef2d7e6203 | wikidoc | Tablet | Tablet
Please Take Over This Page and Apply to be Editor-In-Chief for this topic:
There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
A tablet is a mixture of active substances and excipients, usually in powder form, pressed or compacted into a solid. The excipients include binders, glidants (flow aids) and lubricants to ensure efficient tabletting; disintegrants to ensure that the tablet breaks up in the digestive tract; sweetners or flavours to mask the taste of bad-tasting active ingredients; and pigments to make uncoated tablets visually attractive. A coating may be applied to hide the taste of the tablet's components, to make the tablet smoother and easier to swallow, and to make it more resistant to the environment, extending its shelf life.
Medicines to be taken orally are very often supplied in tablet form; indeed the word tablet without qualification would be taken to refer to a medicinal tablet. Medicinal tablets and capsules are often called pills. Other products are manufactured in the form of tablets which are designed to dissolve or disintegrate; e.g. cleaning and deodorizing products.
Medicinal tablets are usually intended to be swallowed, and are of a suitable size and shape. Tablets for other purposes, e.g., effervescent medicinal tablets and non-medicinal tablets, may be larger.
Medicinal tablets were originally made in the shape of a disk of whatever color their components determined, but are now made in many shapes and colors to help users to distinguish between different medicines that they take. Tablets are often stamped with symbols, letters, and numbers, which enable them to be identified. Sizes of tablets to be swallowed range from a few millimeters to about a centimeter. Some tablets are in the shape of capsules, and are called "caplets".
When Tylenol capsules were laced with cyanide (an incident referred to as the Tylenol scare), many people stopped buying capsules because they are easy to contaminate, in favor of tablets, which are not. Some makers of over-the-counter drugs responded by starting to make what they termed "caplets", which were actually just tablets made in the shape of a capsule.
Tablets are often scored to allow them to be easily broken into equal halves for smaller doses.
Some people have difficulty swallowing tablets, this is called dysphagia. This is often caused by a gag reflex.
# Tabletting formulations
In the tablet-pressing process, it is important that all ingredients be fairly dry, powdered or granular, somewhat uniform in particle size, and freely flowing. Mixed particle sized powders can segregate due to operational vibrations, which can result in tablets with poor drug or active pharmaceutical ingredient (API) content uniformity. Content uniformity ensures that the same API dose is delivered with each tablet.
Some APIs may be tableted as pure substances, but this is rarely the case; most formulations include excipients. Normally, an inactive ingredient (excipient) termed a binder is added to help hold the tablet together and give it strength. A wide variety of binders may be used, some common ones including lactose powder, dibasic calcium phosphate, sucrose, corn (maize) starch, microcrystalline cellulose and modified cellulose (for example hydroxymethyl cellulose).
Often, an ingredient is also needed to act as a disintegrant that hydrates readily in water to aid tablet dispersion once swallowed, releasing the API for absorption. Some binders, such as starch and cellulose, are also excellent disintegrants.
Small amounts of lubricants are usually added, as well. The most common of these is magnesium stearate; however, other commonly used tablet lubricants include stearic acid (stearin), hydrogenated oil, and sodium stearyl fumarate. These help the tablets, once pressed, to be more easily ejected from the die.
# Tablet coating
Many tablets today are coated after being pressed. Although sugar-coating was popular in the past, the process has many drawbacks. Modern tablet coatings are polymer and polysaccharide based, with plasticizers and pigments included. Tablet coatings must be stable and strong enough to survive the handling of the tablet, must not make tablets stick together during the coating process, and must follow the fine contours of embossed characters or logos on tablets. Coatings can also facilitate printing on tablets, if required. Coatings are necessary for tablets that have an unpleasant taste, and a smoother finish makes large tablets easier to swallow. Tablet coatings are also useful to extend the shelf-life of components that are sensitive to moisture or oxidation. Opaque materials like titanium dioxide can protect light-sensitive actives from photodegradation. Special coatings (for example with pearlescent effects) can enhance brand recognition.
If the active ingredient of a tablet is sensitive to acid, or is irritant to the stomach lining, an enteric coating can be used, which is resistant to stomach acid and dissolves in the high pH of the intestines. Enteric coatings are also used for medicines that can be negatively affected by taking a long time to reach the small intestine where they are absorbed. Coatings are often chosen to control the rate of dissolution of the drug in the gastro-intestinal tract. Some drugs will be absorbed better at different points in the digestive system. If the highest percentage of absorption of a drug takes place in the stomach, a coating that dissolves quickly and easily in acid will be selected. If the rate of absorption is best in the large intestine or colon, then a coating that is acid resistant and dissolves slowly would be used to ensure it reached that point before dispersing. The area of the gastro-intestinal tract with the best absorption for any particular drug is usually determined by clinical trials.
# Tablet presses
Tablet presses, also called tabletting machines, range from small, inexpensive bench-top models that make one tablet at a time (single-station presses), no more than a few thousand an hour, and with only around a half-ton pressure, to large, computerized, industrial models (multi-station rotary or eccentric presses) that can make hundreds of thousands to millions of tablets an hour with much greater pressure. Some tablet presses can make extremely large tablets, such as some of the toilet cleaning and deodorizing products or dishwasher soap. Others can make smaller tablets, from regular aspirin to some the size of a bb gun pellet. Tablet presses may also be used to form tablets out of a wide variety of materials, from powdered metals to cookie crumbs. The tablet press is an essential piece of machinery for any pharmaceutical and nutraceutical manufacturer.
# Pill-splitters
It is sometimes necessary to split tablets into halves or quarters. Tablets are easier to break accurately if scored, but there are devices called pill-splitters which cut unscored and scored tablets. Tablets with special coatings (for example enteric coatings or controlled-release coatings) should not be broken before use, as this will expose the tablet core to the digestive juices, short-circuiting the intended delayed-release effect. | Tablet
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# Overview
A tablet is a mixture of active substances and excipients, usually in powder form, pressed or compacted into a solid. The excipients include binders, glidants (flow aids) and lubricants to ensure efficient tabletting; disintegrants to ensure that the tablet breaks up in the digestive tract; sweetners or flavours to mask the taste of bad-tasting active ingredients; and pigments to make uncoated tablets visually attractive. A coating may be applied to hide the taste of the tablet's components, to make the tablet smoother and easier to swallow, and to make it more resistant to the environment, extending its shelf life.
Medicines to be taken orally are very often supplied in tablet form; indeed the word tablet without qualification would be taken to refer to a medicinal tablet. Medicinal tablets and capsules are often called pills. Other products are manufactured in the form of tablets which are designed to dissolve or disintegrate; e.g. cleaning and deodorizing products.
Medicinal tablets are usually intended to be swallowed, and are of a suitable size and shape. Tablets for other purposes, e.g., effervescent medicinal tablets and non-medicinal tablets, may be larger.
Medicinal tablets were originally made in the shape of a disk of whatever color their components determined, but are now made in many shapes and colors to help users to distinguish between different medicines that they take. Tablets are often stamped with symbols, letters, and numbers, which enable them to be identified. Sizes of tablets to be swallowed range from a few millimeters to about a centimeter. Some tablets are in the shape of capsules, and are called "caplets".
When Tylenol capsules were laced with cyanide (an incident referred to as the Tylenol scare), many people stopped buying capsules because they are easy to contaminate, in favor of tablets, which are not. Some makers of over-the-counter drugs responded by starting to make what they termed "caplets", which were actually just tablets made in the shape of a capsule.
Tablets are often scored to allow them to be easily broken into equal halves for smaller doses.
Some people have difficulty swallowing tablets, this is called dysphagia. This is often caused by a gag reflex.
# Tabletting formulations
In the tablet-pressing process, it is important that all ingredients be fairly dry, powdered or granular, somewhat uniform in particle size, and freely flowing. Mixed particle sized powders can segregate due to operational vibrations, which can result in tablets with poor drug or active pharmaceutical ingredient (API) content uniformity. Content uniformity ensures that the same API dose is delivered with each tablet.
Some APIs may be tableted as pure substances, but this is rarely the case; most formulations include excipients. Normally, an inactive ingredient (excipient) termed a binder is added to help hold the tablet together and give it strength. A wide variety of binders may be used, some common ones including lactose powder, dibasic calcium phosphate, sucrose, corn (maize) starch, microcrystalline cellulose and modified cellulose (for example hydroxymethyl cellulose).
Often, an ingredient is also needed to act as a disintegrant that hydrates readily in water to aid tablet dispersion once swallowed, releasing the API for absorption. Some binders, such as starch and cellulose, are also excellent disintegrants.
Small amounts of lubricants are usually added, as well. The most common of these is magnesium stearate; however, other commonly used tablet lubricants include stearic acid (stearin), hydrogenated oil, and sodium stearyl fumarate. These help the tablets, once pressed, to be more easily ejected from the die.
# Tablet coating
Many tablets today are coated after being pressed. Although sugar-coating was popular in the past, the process has many drawbacks. Modern tablet coatings are polymer and polysaccharide based, with plasticizers and pigments included. Tablet coatings must be stable and strong enough to survive the handling of the tablet, must not make tablets stick together during the coating process, and must follow the fine contours of embossed characters or logos on tablets. Coatings can also facilitate printing on tablets, if required. Coatings are necessary for tablets that have an unpleasant taste, and a smoother finish makes large tablets easier to swallow. Tablet coatings are also useful to extend the shelf-life of components that are sensitive to moisture or oxidation. Opaque materials like titanium dioxide can protect light-sensitive actives from photodegradation. Special coatings (for example with pearlescent effects) can enhance brand recognition.
If the active ingredient of a tablet is sensitive to acid, or is irritant to the stomach lining, an enteric coating can be used, which is resistant to stomach acid and dissolves in the high pH of the intestines. Enteric coatings are also used for medicines that can be negatively affected by taking a long time to reach the small intestine where they are absorbed. Coatings are often chosen to control the rate of dissolution of the drug in the gastro-intestinal tract. Some drugs will be absorbed better at different points in the digestive system. If the highest percentage of absorption of a drug takes place in the stomach, a coating that dissolves quickly and easily in acid will be selected. If the rate of absorption is best in the large intestine or colon, then a coating that is acid resistant and dissolves slowly would be used to ensure it reached that point before dispersing. The area of the gastro-intestinal tract with the best absorption for any particular drug is usually determined by clinical trials.
# Tablet presses
Tablet presses, also called tabletting machines, range from small, inexpensive bench-top models that make one tablet at a time (single-station presses), no more than a few thousand an hour, and with only around a half-ton pressure, to large, computerized, industrial models (multi-station rotary or eccentric presses) that can make hundreds of thousands to millions of tablets an hour with much greater pressure. Some tablet presses can make extremely large tablets, such as some of the toilet cleaning and deodorizing products or dishwasher soap. Others can make smaller tablets, from regular aspirin to some the size of a bb gun pellet. Tablet presses may also be used to form tablets out of a wide variety of materials, from powdered metals to cookie crumbs. The tablet press is an essential piece of machinery for any pharmaceutical and nutraceutical manufacturer.
# Pill-splitters
It is sometimes necessary to split tablets into halves or quarters. Tablets are easier to break accurately if scored, but there are devices called pill-splitters which cut unscored and scored tablets. Tablets with special coatings (for example enteric coatings or controlled-release coatings) should not be broken before use, as this will expose the tablet core to the digestive juices, short-circuiting the intended delayed-release effect.
Template:SIB
Template:WH
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Tablet | |
fb18701d8de28f857a8295d6ce78f0aa0d955924 | wikidoc | Tai Ji | Tai Ji
Taiji (太極) is a state of being from Tao and Wuji. It is a state of absolute, and of infinite potentiality. In Tao Te Ching, Tao manifested as One, which is Taiji. In a Taoist guidance book, the same verse was amplified as out of Tao came Taiji, which then split into yin and yang or Two Aspects, yin and yang slitting into the Four Realms, Wu xing the Five Elements, and from there the world was created.
Taiji was a state in which the world became intelligible before creation. Taiji may be equated to the One, Oneness, Unity, as in attaining One or Unity (得一) and as stated in the Tao Te Ching.
# Core concept
Translated as "the great ultimate," the Taiji is understood to be the ideal of existence. Yin and yang represent the contrasting qualities within reality and experience. For example, light contrasts with darkness, providing them both with context and therefore meaning. Taiji is not perceived as a simple list of all things and potential things, but rather a complex interconnection of all things in all possible contexts. This concept is often used to illustrate the doctrine of cosmological unity. It is also used to explain the creation of the "myriad things" (i.e., everything in existence) through the dialectical process of alternating polarity between yin and yang. Western proponents of Taoism sometimes conflate Taiji and the "myriad things," but Taiji is not only representative of what exists, but also that which has existed, will exist, and could potentially exist.
# Taiji in historical China
The concept of Taiji was introduced in the Zhuang Zi, showing its early place in Taoism. It also appears in the Xì Cí (Great Appendix) of the I Ching, a fundamental Taoist classic.
When Confucianism came to the fore again during the Song Dynasty as Neo-Confucianism, it synthesized aspects of Chinese Buddhism and Taoism, and drew them together using threads that traced back to the metaphysical discussions in the Book of Changes.
# See Also
- Taegeuk
- Tomoe
- Wuji
- Xiuzhen
# Notes
- ↑ Tao te Ching Chapter 42 : 道生一。一生二。二生三。三生萬物
- ↑ Tiantang Yiuchi Chapter 4 : 原由無極 (Wuji) 元始一動而生太極 (Taiji)，太極含兩儀 (two aspects) 陰陽 (yin and yang)，而化三才四象 (Four Realms) 五行(Wu xing)……。
- ↑ Robinet (1981), p. 16.
- ↑ Tao Te Ching Chapter 39 : 昔之得一者。天得一以清。地得一以寧。神得一以靈。谷得一以盈。萬物得一以生。
- ↑ Chen, Ellen M. (1989). The Tao Te Ching: A New Translation and Commentary. St. Paul Minnesota: Paragon House.
# Reference
- Robinet, Isabelle. Taoism: Growth of a Religion (Stanford: Stanford University Press, 1997 ) page 103. ISBN 0-8047-2839-9. | Tai Ji
Template:Contains Chinese text
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Template:Taoism portal
Taiji (太極) is a state of being from Tao and Wuji. It is a state of absolute, and of infinite potentiality. In Tao Te Ching, Tao manifested as One, which is Taiji[1]. In a Taoist guidance book, the same verse was amplified as out of Tao came Taiji, which then split into yin and yang or Two Aspects, yin and yang slitting into the Four Realms, Wu xing the Five Elements, and from there the world was created[2].
Taiji was a state in which the world became intelligible before creation. Taiji may be equated to the One, Oneness, Unity, as in attaining One or Unity (得一) [3] and as stated in the Tao Te Ching[4].
# Core concept
Translated as "the great ultimate,"[5] the Taiji is understood to be the ideal of existence. Yin and yang represent the contrasting qualities within reality and experience. For example, light contrasts with darkness, providing them both with context and therefore meaning. Taiji is not perceived as a simple list of all things and potential things, but rather a complex interconnection of all things in all possible contexts. This concept is often used to illustrate the doctrine of cosmological unity. It is also used to explain the creation of the "myriad things" (i.e., everything in existence) through the dialectical process of alternating polarity between yin and yang. Western proponents of Taoism sometimes conflate Taiji and the "myriad things," but Taiji is not only representative of what exists, but also that which has existed, will exist, and could potentially exist.
# Taiji in historical China
The concept of Taiji was introduced in the Zhuang Zi, showing its early place in Taoism. It also appears in the Xì Cí (Great Appendix) of the I Ching, a fundamental Taoist classic.
When Confucianism came to the fore again during the Song Dynasty as Neo-Confucianism, it synthesized aspects of Chinese Buddhism and Taoism, and drew them together using threads that traced back to the metaphysical discussions in the Book of Changes.
# See Also
- Taegeuk
- Tomoe
- Wuji
- Xiuzhen
# Notes
- ↑ Tao te Ching Chapter 42 : 道生一。一生二。二生三。三生萬物
- ↑ Tiantang Yiuchi Chapter 4 : 原由無極 (Wuji) 元始一動而生太極 (Taiji)，太極含兩儀 (two aspects) 陰陽 (yin and yang)，而化三才四象 (Four Realms) 五行(Wu xing)……。
- ↑ Robinet (1981), p. 16.
- ↑ Tao Te Ching Chapter 39 : 昔之得一者。天得一以清。地得一以寧。神得一以靈。谷得一以盈。萬物得一以生。
- ↑ Chen, Ellen M. (1989). The Tao Te Ching: A New Translation and Commentary. St. Paul Minnesota: Paragon House.
# Reference
- Robinet, Isabelle. Taoism: Growth of a Religion (Stanford: Stanford University Press, 1997 [original French 1992]) page 103. ISBN 0-8047-2839-9.
# External Links
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ar:تاي تشي
de:Taiji
zh-classical:太極
ko:태극
sk:Tchaj-ťi
sv:Taiji
Template:WikiDOc Sources
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Tai_Ji | |
7c9dc615970081b2501ee8010088835aff1e4ac0 | wikidoc | Tallow | Tallow
Tallow is a rendered form of beef or mutton fat, processed from suet. Unlike suet, tallow can be stored for extended periods without the need for refrigeration to prevent decomposition, provided it is kept in an airtight container to prevent oxidation.
Rendered fat obtained from pigs is known as lard.
# Uses
It is used in animal feed, to make soap, for cooking, and as a bird food. It can be used as a raw material for the production of biodiesel and other oleochemicals. Historically, it was used to make tallow candles, which were a cheaper alternative to wax candles.
Industrially, tallow is not strictly defined as beef or mutton fat. In this context, tallow is animal fat that conforms to certain technical criteria, including its melting point, which is also known as titre. It is common for commercial tallow to contain fat derived from other animals, such as pigs.
Amid concerns in the 1990s over high cholesterol content, and protests from Hindus (many of whom do not consume food derived from beef) and vegetarians, McDonald's french fries were cooked in a mixture 93% beef tallow and 7% cottonseed oil.
Tallow is used in the steel rolling industry to provide the required lubrication as the sheet steel is compressed through the steel rollers. There is a trend towards replacing tallow based lubrication with synthetic oils in rolling applications for surface cleanliness reasons.
Tallow can also be used as flux for soldering.
# Composition
The composition of the fatty acids is typically as follows:
- Saturated fatty acids:
Palmitic acid: 26 %
Stearic acid: 14 %
Myristic acid: 3 %
- Palmitic acid: 26 %
- Stearic acid: 14 %
- Myristic acid: 3 %
- Monounsaturated fatty acids:
Oleic acid: 47 %
Palmitoleic acid: 3 %
- Oleic acid: 47 %
- Palmitoleic acid: 3 %
- Polyunsaturated fatty acids:
Linoleic acid: 3 %
Linolenic acid: 1 %
- Linoleic acid: 3 %
- Linolenic acid: 1 % | Tallow
Tallow is a rendered form of beef or mutton fat, processed from suet. Unlike suet, tallow can be stored for extended periods without the need for refrigeration to prevent decomposition, provided it is kept in an airtight container to prevent oxidation.
Rendered fat obtained from pigs is known as lard.
# Uses
It is used in animal feed, to make soap, for cooking, and as a bird food. It can be used as a raw material for the production of biodiesel and other oleochemicals. Historically, it was used to make tallow candles, which were a cheaper alternative to wax candles.
Industrially, tallow is not strictly defined as beef or mutton fat. In this context, tallow is animal fat that conforms to certain technical criteria, including its melting point, which is also known as titre. It is common for commercial tallow to contain fat derived from other animals, such as pigs.
Amid concerns in the 1990s over high cholesterol content, and protests from Hindus (many of whom do not consume food derived from beef) and vegetarians, McDonald's french fries were cooked in a mixture 93% beef tallow and 7% cottonseed oil.[1]
Tallow is used in the steel rolling industry to provide the required lubrication as the sheet steel is compressed through the steel rollers. There is a trend towards replacing tallow based lubrication with synthetic oils in rolling applications for surface cleanliness reasons.[2]
Tallow can also be used as flux for soldering.[3]
# Composition
Template:Nutritionalvalue
The composition of the fatty acids is typically as follows:[4]
- Saturated fatty acids:
Palmitic acid: 26 %
Stearic acid: 14 %
Myristic acid: 3 %
- Palmitic acid: 26 %
- Stearic acid: 14 %
- Myristic acid: 3 %
- Monounsaturated fatty acids:
Oleic acid: 47 %
Palmitoleic acid: 3 %
- Oleic acid: 47 %
- Palmitoleic acid: 3 %
- Polyunsaturated fatty acids:
Linoleic acid: 3 %
Linolenic acid: 1 %
- Linoleic acid: 3 %
- Linolenic acid: 1 % | https://www.wikidoc.org/index.php/Tallow | |
03fcff518050ccbc7226e72267d1db6023766278 | wikidoc | Tampon | Tampon
A tampon is a plug of cotton or other absorbent material inserted into a body cavity or wound to absorb fluid. The most common type in daily use (and the topic of the remainder of this article) is a usually disposable plug that is designed to be inserted into the vagina during menstruation to absorb the flow of blood. The use of these devices has occasionally caused infection and (rarely) death (see Toxic shock syndrome). In the United States, the Food and Drug Administration (FDA) regulates tampons as medical devices.
# History
As a medical device, the tampon (from the French for plug, or stopper) has been around since the 19th century, when antiseptic cotton tampons treated with salicylates were used to stop the bleeding from bullet wounds, and there have been reports of modern menstrual tampons being used for the same purpose by soldiers in the Iraq War.
The tampon with an applicator and string was invented in 1929 and submitted for patent in 1931 by Dr. Earle Haas, an American from Denver, Colorado. Tampons based on Dr. Haas' design were first sold in the U.S. in 1936. Later, the expansible tampon was invented in 1974 (patent in 1976) by world-renowned obstetrician/gynaecologist, Dr. Kermit E Krantz.
# Design and packaging
Tampons come in various sizes, which are related to their absorbency ratings and packaging.
The shape of all tampons is basically the same; long oval cylinders. Tampons sold in the United States are made of cotton, rayon, or a blend of the two. Tampons are sold individually wrapped to keep them clean, although they are not sterile, nor are tampon companies required by law to list the ingredients in them. They have a string for ease of removal, and may be packaged inside an applicator to aid insertion.
Tampon applicators may be made of plastic or cardboard, and are similar in design to a syringe. The applicator consists of a bigger tube and a narrower tube. The bigger tube has a smooth surface and a round end for easier insertion. Some applicators have a star shape opening at the round end, others are open ended. The tampon itself rests inside the bigger tube, near the open end. The narrower tube is nested inside the other end of the bigger tube. The open end of the bigger tube is placed and held in the vagina, then the narrower tube is pushed into the bigger tube (typically using a finger) pushing the tampon through and into the vagina. If not inserted at a 45 degree angle it can cause discomfort and make removal difficult.
Digital or non-applicator tampons are tampons sold without applicators; these are simply unwrapped and pushed into the vagina with the fingers (digits).
Probiotic tampons are available in Europe. These tampons can help prevent or cure vaginal infections, like Bacterial Vaginosis and/ or Candida, by strengthening the natural microbiotic vaginal flora. These tampons include probiotics, or three strains of lactic acid bacteria, which naturally occur in the healthy vagina. The vaginal flora of a healthy woman is dominated by lactic acid bacteria, which produce lactic acid as part of their metabolism. The lactic acid makes the vagina acidic, about pH 3.8 to 4.2. Most pathogens do not thrive in such an acidic environment. Therefore, lactic acid bacteria are part of the human female's first line of defense against infection.
It is not normally necessary to remove a tampon before urinating or having a bowel movement.
# Absorbency ratings
Tampons are available in several different absorbency ratings, which are consistent across manufacturers in the U.S.:
- Junior absorbency: 6 grams and under
- Regular absorbency: 6 to 9 grams
- Super absorbency: 9 to 12 grams
- Super plus absorbency: 12 to 15 grams
- Ultra absorbency: 15 to 18 grams
# Toxic shock syndrome
Tampons have been shown to have a connection to toxic shock syndrome (TSS), a rare but sometimes fatal disease caused by bacterial infection. The U.S. FDA suggests the following guidelines for decreasing the risk of contracting TSS when using tampons:
- Follow package directions for insertion
- Choose the lowest absorbency for your flow
- Change your tampon at least every 4 to 8 hours
- Consider alternating disposable or cloth pads with tampons
- Avoid tampon usage overnight when sleeping
- Know the warning signs of toxic shock syndrome
- Don't use tampons between periods
Following these guidelines can help to protect a woman from TSS, and cases of tampon connected TSS are extremely rare in the United States.
# Other health concerns
Many chemicals are present in tampons, including pesticides used on the cotton and chlorine used to bleach the tampons. Some of the chemicals used to bleach tampons have been implicated in the formation of dioxin. A study by the FDA done in 1995 says there are not significant amounts of dioxin to pose a health risk; the amount detected ranged from undetectable to 1 part in 3 trillion, which is far less than the normal exposure to dioxin in everyday life. However, the presence of dioxin in a product that enters a major body orifice, where there is more risk of absorption, caused a great deal of concern. Nevertheless, manufacturers insist that bleaching is needed to produce effective products, despite tampons not using bleaching or chemical treatment being available.
Another concern is related to the use of rayon in tampons. Rayon consists of tiny strings of plastic. Some speculate that these strands of plastic can cause microtears on the vaginal wall when inserted and taking out. There is further speculation that, if microtears are present, the condition could leave the vagina more open to infection.
Although some say that 100% cotton tampons may be safer than using tampons with a cotton and rayon mix because of there being less dioxin, there is still a risk with all-cotton tampons. All-cotton tampons are generally harder to find and usually cost more than generic tampon brands. Some researchers claim that although switching to a 100% cotton alternative reduces the risk of TSS, it does not remove it entirely. We are also exposed to dioxins in other ways, so eliminating dioxin in tampons will not mean there will be no contact with dioxin in the environment.
Fiber loss along with damage done to the vaginal tissue from fiber has also been a concern, but fiber loss is more likely with all-cotton tampons. Furthermore, as tampons are absorbent and placed within an area such as the vagina, this significantly increases the risk of bacterial infections.
# Alternative choices
Prior to the development of tampons, Western women generally resorted to reusable cloth rags. These would be soaked in a diaper pail after use. Rags continue to be used by women in Third-World countries today, including much of Africa, out of affordability and distribution problems associated with other methods.
The Museum of Menstruation proposes that most premodern women used nothing at all, but bled into their clothing. It should also be remembered that many premodern women would have menstruated relatively little, being pregnant or breast-feeding most of their fertile lives.
In some cultures, the use of tampons by virgins is discouraged for fear of damaging their hymens (regarded as proof of virginity), or habituating them to the act of penetration. A satire by Landover Baptist Church alludes to such mores in a mock-sermon "Tampons: Satan's Little Cotton Fingers."
Most of the world's women today use methods other than tampons for absorbing menstrual fluid. Women in East Asia generally use pads.
Environmentally conscious women may be interested in menstral cups (such as the keeper cup) or reusable glad rags, because they create less waste. Other alternatives to standard tampons include organic tampons (made from organic cotton) and home-made tampons.
Non-tampon alternatives include the following:
## Disposable
- disposable menstrual pads (sanitary napkins/towels)
- organic menstrual pads (sanitary napkins/towels)
- Diaphragm-style menstrual cups
## Reusable
- Menstrual cup made of silicone, or gum rubber. (Examples include the DivaCup and The Keeper/Moon Cup).
- diaphragm as menstrual cup
- cloth menstrual pads
- homemade menstrual pads
- Free-flow (layering or instinctive )
- padded panties/period pants/Lunapanties
- sea sponges (used like tampons) | Tampon
A tampon is a plug of cotton or other absorbent material inserted into a body cavity or wound to absorb fluid. The most common type in daily use (and the topic of the remainder of this article) is a usually disposable plug that is designed to be inserted into the vagina during menstruation to absorb the flow of blood. The use of these devices has occasionally caused infection and (rarely) death (see Toxic shock syndrome). In the United States, the Food and Drug Administration (FDA) regulates tampons as medical devices.
# History
As a medical device, the tampon (from the French for plug, or stopper[1]) has been around since the 19th century, when antiseptic cotton tampons treated with salicylates were used to stop the bleeding from bullet wounds[2], and there have been reports of modern menstrual tampons being used for the same purpose by soldiers in the Iraq War[3].
The tampon with an applicator and string was invented in 1929 and submitted for patent in 1931 by Dr. Earle Haas, an American from Denver, Colorado. Tampons based on Dr. Haas' design were first sold in the U.S. in 1936. Later, the expansible tampon was invented in 1974 (patent in 1976) by world-renowned obstetrician/gynaecologist, Dr. Kermit E Krantz.
# Design and packaging
Tampons come in various sizes, which are related to their absorbency ratings and packaging.
The shape of all tampons is basically the same; long oval cylinders. Tampons sold in the United States are made of cotton, rayon, or a blend of the two. Tampons are sold individually wrapped to keep them clean, although they are not sterile, nor are tampon companies required by law to list the ingredients in them. They have a string for ease of removal, and may be packaged inside an applicator to aid insertion.
Tampon applicators may be made of plastic or cardboard, and are similar in design to a syringe. The applicator consists of a bigger tube and a narrower tube. The bigger tube has a smooth surface and a round end for easier insertion. Some applicators have a star shape opening at the round end, others are open ended. The tampon itself rests inside the bigger tube, near the open end. The narrower tube is nested inside the other end of the bigger tube. The open end of the bigger tube is placed and held in the vagina, then the narrower tube is pushed into the bigger tube (typically using a finger) pushing the tampon through and into the vagina. If not inserted at a 45 degree angle it can cause discomfort and make removal difficult.
Digital or non-applicator tampons are tampons sold without applicators; these are simply unwrapped and pushed into the vagina with the fingers (digits).
Probiotic tampons are available in Europe. These tampons can help prevent or cure vaginal infections, like Bacterial Vaginosis and/ or Candida, by strengthening the natural microbiotic vaginal flora. These tampons include probiotics, or three strains of lactic acid bacteria, which naturally occur in the healthy vagina. The vaginal flora of a healthy woman is dominated by lactic acid bacteria, which produce lactic acid as part of their metabolism. The lactic acid makes the vagina acidic, about pH 3.8 to 4.2. Most pathogens do not thrive in such an acidic environment. Therefore, lactic acid bacteria are part of the human female's first line of defense against infection.
It is not normally necessary to remove a tampon before urinating or having a bowel movement.
# Absorbency ratings
Tampons are available in several different absorbency ratings, which are consistent across manufacturers in the U.S.:
- Junior absorbency: 6 grams and under
- Regular absorbency: 6 to 9 grams
- Super absorbency: 9 to 12 grams
- Super plus absorbency: 12 to 15 grams
- Ultra absorbency: 15 to 18 grams
# Toxic shock syndrome
Tampons have been shown to have a connection to toxic shock syndrome (TSS), a rare but sometimes fatal disease caused by bacterial infection. The U.S. FDA suggests the following guidelines for decreasing the risk of contracting TSS when using tampons:
- Follow package directions for insertion
- Choose the lowest absorbency for your flow
- Change your tampon at least every 4 to 8 hours
- Consider alternating disposable or cloth pads with tampons
- Avoid tampon usage overnight when sleeping
- Know the warning signs of toxic shock syndrome
- Don't use tampons between periods
Following these guidelines can help to protect a woman from TSS, and cases of tampon connected TSS are extremely rare in the United States.
# Other health concerns
Many chemicals are present in tampons, including pesticides used on the cotton and chlorine used to bleach the tampons. Some of the chemicals used to bleach tampons have been implicated in the formation of dioxin. A study by the FDA done in 1995 says there are not significant amounts of dioxin to pose a health risk; the amount detected ranged from undetectable to 1 part in 3 trillion, which is far less than the normal exposure to dioxin in everyday life.[1] However, the presence of dioxin in a product that enters a major body orifice, where there is more risk of absorption, caused a great deal of concern. Nevertheless, manufacturers insist that bleaching is needed to produce effective products, despite tampons not using bleaching or chemical treatment being available.
Another concern is related to the use of rayon in tampons. Rayon consists of tiny strings of plastic. Some speculate that these strands of plastic can cause microtears on the vaginal wall when inserted and taking out. There is further speculation that, if microtears are present, the condition could leave the vagina more open to infection.
Although some say that 100% cotton tampons may be safer than using tampons with a cotton and rayon mix because of there being less dioxin, there is still a risk with all-cotton tampons. All-cotton tampons are generally harder to find and usually cost more than generic tampon brands. Some researchers claim that although switching to a 100% cotton alternative reduces the risk of TSS, it does not remove it entirely. We are also exposed to dioxins in other ways, so eliminating dioxin in tampons will not mean there will be no contact with dioxin in the environment.
Fiber loss along with damage done to the vaginal tissue from fiber has also been a concern, but fiber loss is more likely with all-cotton tampons. Furthermore, as tampons are absorbent and placed within an area such as the vagina, this significantly increases the risk of bacterial infections.
# Alternative choices
Prior to the development of tampons, Western women generally resorted to reusable cloth rags. These would be soaked in a diaper pail after use. Rags continue to be used by women in Third-World countries today, including much of Africa, out of affordability and distribution problems associated with other methods.
The Museum of Menstruation proposes that most premodern women used nothing at all, but bled into their clothing. It should also be remembered that many premodern women would have menstruated relatively little, being pregnant or breast-feeding most of their fertile lives.
In some cultures, the use of tampons by virgins is discouraged for fear of damaging their hymens (regarded as proof of virginity), or habituating them to the act of penetration.[citation needed] A satire by Landover Baptist Church alludes to such mores in a mock-sermon "Tampons: Satan's Little Cotton Fingers."
Most of the world's women today use methods other than tampons for absorbing menstrual fluid. Women in East Asia generally use pads.[citation needed]
Environmentally conscious women may be interested in menstral cups (such as the keeper cup) or reusable glad rags, because they create less waste. Other alternatives to standard tampons include organic tampons (made from organic cotton) and home-made tampons.
Non-tampon alternatives include the following:
## Disposable
- disposable menstrual pads (sanitary napkins/towels)
- organic menstrual pads (sanitary napkins/towels)
- Diaphragm-style menstrual cups
## Reusable
- Menstrual cup made of silicone, or gum rubber. (Examples include the DivaCup and The Keeper/Moon Cup).
- diaphragm as menstrual cup
- cloth menstrual pads
- homemade menstrual pads
- Free-flow (layering [using layers of clothing to avoid obvious leaking] or instinctive [learning to recognize when you will bleed])
- padded panties/period pants/Lunapanties
- sea sponges (used like tampons) | https://www.wikidoc.org/index.php/Tampon | |
ff3a935c9578aa93a4cc56c6ce86f2ba184b4de8 | wikidoc | Tannin | Tannin
Tannins are astringent, bitter-tasting plant polyphenols that bind and precipitate proteins. The term tannin refers to the use of tannins in tanning animal hides into leather; however, the term is widely applied to any large polyphenolic compound containing sufficient hydroxyls and other suitable groups (such as carboxyls) to form strong complexes with proteins and other macromolecules. Tannins have molecular weights ranging from 500 to over 3,000.
Tannins are usually divided into hydrolyzable tannins and condensed tannins (proanthocyanidins).
# Hydrolyzable Tannins
At the center of a hydrolyzable tannin molecule, there is a polyol carbohydrate (usually D-glucose). The hydroxyl groups of the carbohydrate are partially or totally esterified with phenolic groups such as gallic acid (in gallotannins) or ellagic acid (in ellagitannins). Hydrolyzable tannins are hydrolyzed by weak acids or weak bases to produce carbohydrate and phenolic acids.
Examples of gallotannins are the gallic acid esters of glucose in tannic acid (C76H52O46), found in the leaves and bark of many plant species.
# Condensed Tannins
Condensed tannins, also known as proanthocyanidins, are polymers of 2 to 50 (or more) flavonoid units that are joined by carbon-carbon bonds, which are not susceptible to being cleaved by hydrolysis. While hydrolyzable tannins and most condensed tannins are water soluble, some very large condensed tannins are insoluble.
# Foods with tannins
## Tea
The tea plant (Camellia sinensis) is an example of a plant said to have a naturally high tannin content. When any type of tea leaf is steeped in hot water it brews a "tart" (astringent) flavour that is characteristic of tannins. This is due to the catechins and other flavonoids. Tea "tannins" are chemically distinct from other types of plant tannins such as tannic acid and tea extracts have been reported to contain no tannic acid.
## Wine
Tannins (mainly condensed tannins) are also found in wine, particularly red wine. Tannins in wine can come from many sources and the tactile properties differ depending on the source. Tannins in grape skins and seeds (the latter being especially harsh) tend to be more noticeable in red wines, which are fermented while in contact with the skins and seeds. Tannins extracted from grapes are condensed tannins, which are polymers of procyanidin monomers. Hydrolysable tannins are extracted from the oak wood the wine is aged in. Hydrolysable tannins are more easily oxidised than condensed tannins.
Modern winemakers take great care to minimize undesirable tannins from seeds by crushing grapes gently to extract their juice. Pressing the grapes results in press wine which is more tannic and might be kept separately. Wines can also take on tannins if matured in oak or wood casks with a high tannin content. Tannins play an important role in preventing oxidation in aging wine and appear to polymerize and make up a major portion of the sediment in wine.
Recently, a study in wine production and consumption has shown that tannins in the form of procyanidins, have a beneficial effect on vascular health. The study showed that tannins suppressed production of the peptide responsible for hardening arteries. To support their findings, the study also points out that wines from the regions of southwest France and Sardinia are particularly rich in procyanidins, and that these regions also produce populations with longer life spans.
## Fruits
### Pomegranates
Pomegranates contain a diverse array of tannins, particularly hydrolysable tannins. The most abundant of pomegranate tannins are called punicalagins. Punicalagins have a molecular weight of 1038 and are the largest molecule found intact in rat plasma after oral ingestion and were found to show no toxic effects in rats who were given a 6% diet of punicalagins for 37 days.. Punicalagins are also found to be the major component responsible for pomegranate juice's antioxidant and health benefits
Several dietary supplements and nutritional ingredients are available that contain extracts of whole pomegranate and/or are standardized to punicalagins, the marker compound of pomegranate. Extracts of pomegranate are also Generally Recognized as Safe (GRAS) by the United States Food and Drug Administration.
It has been recommended to look for pomegranate ingredients that mimic the polyphenol ratio of the fruit, as potent synergistic effects have been observed in 'natural spectrum' extracts, especially pomegranate concentrate normalized to punicalagins.
### Persimmons
Some persimmons are highly astringent and therefore inedible when they are not extremely ripe (specifically the Korean, American, and Hachiya or Japanese). This is due to the high level of tannins, and if eaten by humans (and many other animals), the mouth will become completely dry, yet the saliva glands will continue to secrete saliva which cannot affect the tannin-laced food. Areca Catechu also contains tannin which contributes to its antibacterial properties
### Berries
Most berries, such as cranberries strawberries and blueberries, contain both hydrolyzable and condensed tannins.
# Nutrition
If ingested in excessive quantities, tannins inhibit the absorption of minerals such as iron into the body. This is because tannins are metal ion chelators, and tannin-chelated metal ions are not bioavailable. This may not be bad for someone with an infection, as iron is mopped up by the immune system to keep microorganisms from properly multiplying. Tannins have been shown to precipitate proteins, which inhibits in some ruminant animals the absorption of nutrients from high-tannin grains such as sorghum.
# Uses
Tannins are an important ingredient in the process of tanning leather. Oak bark has traditionally been the primary source of tannery tannin, though inorganic tanning agents are also in use today.
Tannins may be employed medicinally in antidiarrheal, hemostatic, and antihemorrhoidal compounds.
Tannins produce different colors with ferric chloride (either blue, blue black, or green to greenish black) according to the type of tannin. Iron gall ink is produced by treating a solution of tannins with iron(II) sulfate.
Tannin is a component in a type of industrial particleboard adhesive developed jointly by the Tanzania Industrial Research and Development Organization and Forintek Labs Canada.
# Potential Medical
Tannins, including gallo and ellagic acid (epigallitannins), are inhibitors of HIV replication.
- 1,3,4-Tri-O-galloylquinic acid
- 3,5-di-O-galloyl-shikimic acid,
- 3,4,5-tri-O-galloylshikimic acid
- punicalin
- punicalagin
inhibited HIV replication in infected H9 lymphocytes with little cytotoxicity. Two compounds, punicalin and punicacortein C, inhibited purified HIV reverse transcriptase. | Tannin
Tannins are astringent, bitter-tasting plant polyphenols that bind and precipitate proteins. The term tannin refers to the use of tannins in tanning animal hides into leather; however, the term is widely applied to any large polyphenolic compound containing sufficient hydroxyls and other suitable groups (such as carboxyls) to form strong complexes with proteins and other macromolecules. Tannins have molecular weights ranging from 500 to over 3,000.[1]
Tannins are usually divided into hydrolyzable tannins and condensed tannins (proanthocyanidins).
# Hydrolyzable Tannins
At the center of a hydrolyzable tannin molecule, there is a polyol carbohydrate (usually D-glucose). The hydroxyl groups of the carbohydrate are partially or totally esterified with phenolic groups such as gallic acid (in gallotannins) or ellagic acid (in ellagitannins). Hydrolyzable tannins are hydrolyzed by weak acids or weak bases to produce carbohydrate and phenolic acids.
Examples of gallotannins are the gallic acid esters of glucose in tannic acid (C76H52O46), found in the leaves and bark of many plant species.
# Condensed Tannins
Condensed tannins, also known as proanthocyanidins, are polymers of 2 to 50 (or more) flavonoid units that are joined by carbon-carbon bonds, which are not susceptible to being cleaved by hydrolysis. While hydrolyzable tannins and most condensed tannins are water soluble, some very large condensed tannins are insoluble.
# Foods with tannins
## Tea
The tea plant (Camellia sinensis) is an example of a plant said to have a naturally high tannin content. When any type of tea leaf is steeped in hot water it brews a "tart" (astringent) flavour that is characteristic of tannins. This is due to the catechins and other flavonoids. Tea "tannins" are chemically distinct from other types of plant tannins such as tannic acid[2] and tea extracts have been reported to contain no tannic acid[3].
## Wine
Tannins (mainly condensed tannins) are also found in wine, particularly red wine. Tannins in wine can come from many sources and the tactile properties differ depending on the source. Tannins in grape skins and seeds (the latter being especially harsh) tend to be more noticeable in red wines, which are fermented while in contact with the skins and seeds. Tannins extracted from grapes are condensed tannins, which are polymers of procyanidin monomers. Hydrolysable tannins are extracted from the oak wood the wine is aged in. Hydrolysable tannins are more easily oxidised than condensed tannins.
Modern winemakers take great care to minimize undesirable tannins from seeds by crushing grapes gently to extract their juice. Pressing the grapes results in press wine which is more tannic and might be kept separately. Wines can also take on tannins if matured in oak or wood casks with a high tannin content. Tannins play an important role in preventing oxidation in aging wine and appear to polymerize and make up a major portion of the sediment in wine.
Recently, a study in wine production and consumption has shown that tannins in the form of procyanidins, have a beneficial effect on vascular health. The study showed that tannins suppressed production of the peptide responsible for hardening arteries. To support their findings, the study also points out that wines from the regions of southwest France and Sardinia are particularly rich in procyanidins, and that these regions also produce populations with longer life spans.[4]
## Fruits
### Pomegranates
Pomegranates contain a diverse array of tannins, particularly hydrolysable tannins. The most abundant of pomegranate tannins are called punicalagins. Punicalagins have a molecular weight of 1038 and are the largest molecule found intact in rat plasma after oral ingestion[5] and were found to show no toxic effects in rats who were given a 6% diet of punicalagins for 37 days.[6]. Punicalagins are also found to be the major component responsible for pomegranate juice's antioxidant and health benefits [7]
Several dietary supplements and nutritional ingredients are available that contain extracts of whole pomegranate and/or are standardized to punicalagins, the marker compound of pomegranate. Extracts of pomegranate are also Generally Recognized as Safe (GRAS) by the United States Food and Drug Administration.
It has been recommended to look for pomegranate ingredients that mimic the polyphenol ratio of the fruit, as potent synergistic effects have been observed in 'natural spectrum' extracts, especially pomegranate concentrate normalized to punicalagins.[8]
### Persimmons
Some persimmons are highly astringent and therefore inedible when they are not extremely ripe (specifically the Korean, American, and Hachiya or Japanese). This is due to the high level of tannins, and if eaten by humans (and many other animals), the mouth will become completely dry, yet the saliva glands will continue to secrete saliva which cannot affect the tannin-laced food. Areca Catechu also contains tannin which contributes to its antibacterial properties
### Berries
Most berries, such as cranberries[9] strawberries and blueberries,[10] contain both hydrolyzable and condensed tannins.
# Nutrition
If ingested in excessive quantities, tannins inhibit the absorption of minerals such as iron into the body. This is because tannins are metal ion chelators, and tannin-chelated metal ions are not bioavailable. This may not be bad for someone with an infection, as iron is mopped up by the immune system to keep microorganisms from properly multiplying. Tannins have been shown to precipitate proteins,[1] which inhibits in some ruminant animals the absorption of nutrients from high-tannin grains such as sorghum.
# Uses
Tannins are an important ingredient in the process of tanning leather. Oak bark has traditionally been the primary source of tannery tannin, though inorganic tanning agents are also in use today.
Tannins may be employed medicinally in antidiarrheal, hemostatic, and antihemorrhoidal compounds.
Tannins produce different colors with ferric chloride (either blue, blue black, or green to greenish black) according to the type of tannin. Iron gall ink is produced by treating a solution of tannins with iron(II) sulfate.
Tannin is a component in a type of industrial particleboard adhesive developed jointly by the Tanzania Industrial Research and Development Organization and Forintek Labs Canada.
# Potential Medical
Tannins, including gallo and ellagic acid (epigallitannins), are inhibitors of HIV replication.
- 1,3,4-Tri-O-galloylquinic acid
- 3,5-di-O-galloyl-shikimic acid,
- 3,4,5-tri-O-galloylshikimic acid
- punicalin
- punicalagin
inhibited HIV replication in infected H9 lymphocytes with little cytotoxicity. Two compounds, punicalin and punicacortein C, inhibited purified HIV reverse transcriptase.[11] | https://www.wikidoc.org/index.php/Tannin | |
6c92950acd2e7f801569f296c3939cca1fa98306 | wikidoc | TaqMan | TaqMan
In molecular biology, quantitative real time PCR methods using a dual-labelled fluorogenic probe called a TaqMan probe is a rapid fluorophore-based real-time PCR method . The TaqMan Real-time PCR measures accumulation of a product via the fluorophore during the exponential stages of the PCR, rather than at the end point as in conventional PCR. The exponential increase of the product is used to determine the threshold cycle, CT, i.e. the number of PCR cycles at which a significant exponential increase in fluorescence is detected, and which is directly correlated with the number of copies of DNA template present in the reaction.
The set up of the reaction is very similar to a conventional PCR, but is carried out in a real-time thermal cycler that allows measurement of fluorescent molecules in the PCR tubes. Different from regular PCR, in TaqMan real-time PCR a probe is added to the reaction, i.e., a single-stranded oligonucleotide complementary to a segment of 20-60 nucleotides within the DNA template and located between the two primers. A fluorescent reporter or fluorophore (e.g., 6-carboxyfluorescein, acronym: FAM, or tetrachlorofluorescin, acronym: TET) and quencher (e.g., tetramethylrhodamine, acronym: TAMRA, of dihydrocyclopyrroloindole tripeptide ‘’minor groove binder’’, acronym: MGB) are covalently attached to the 5' and 3' ends of the probe , respectively. The close proximity between fluorophore and quencher attached to the probe inhibits fluorescence from the fluorophore. During PCR, as DNA synthesis commences, the 5' to 3' exonuclease activity of the Taq polymerase degrades that proportion of the probe that has annealed to the template (hence its name: Taq polymerase + PacMan). Degradation of the probe releases the fluorophore from it and breaks the close proximity to the quencher, thus relieving the quenching effect and allowing fluorescence of the fluorophore. Hence, fluorescence detected in the real-time PCR thermal cycler is directly proportional to the fluorophore released and the amount of DNA template present in the PCR.
# Real Time Thermal Cycler
A real-time PCR cycler has a lid with built-in fiber optic cables that measure the fluorescence in the reaction tubes (using laser beams for excitation and detection of the fluorescent emission from the fluorophore). Fluorescence intensities are logged and data stored at each PCR cycle, and then used to create amplification plots of ΔRn (fluorescent signal detected - background) vs cycle number to identify the threshold cycle, CT, which is used to quantitatively determine the amount of DNA template present in the PCR. | TaqMan
In molecular biology, quantitative real time PCR methods using a dual-labelled fluorogenic probe called a TaqMan probe is a rapid fluorophore-based real-time PCR method [1]. The TaqMan Real-time PCR measures accumulation of a product via the fluorophore during the exponential stages of the PCR, rather than at the end point as in conventional PCR. The exponential increase of the product is used to determine the threshold cycle, CT, i.e. the number of PCR cycles at which a significant exponential increase in fluorescence is detected, and which is directly correlated with the number of copies of DNA template present in the reaction.
The set up of the reaction is very similar to a conventional PCR, but is carried out in a real-time thermal cycler that allows measurement of fluorescent molecules in the PCR tubes. Different from regular PCR, in TaqMan real-time PCR a probe is added to the reaction, i.e., a single-stranded oligonucleotide complementary to a segment of 20-60 nucleotides within the DNA template and located between the two primers. A fluorescent reporter or fluorophore (e.g., 6-carboxyfluorescein, acronym: FAM, or tetrachlorofluorescin, acronym: TET) and quencher (e.g., tetramethylrhodamine, acronym: TAMRA, of dihydrocyclopyrroloindole tripeptide ‘’minor groove binder’’, acronym: MGB) are covalently attached to the 5' and 3' ends of the probe , respectively[2]. The close proximity between fluorophore and quencher attached to the probe inhibits fluorescence from the fluorophore. During PCR, as DNA synthesis commences, the 5' to 3' exonuclease activity of the Taq polymerase degrades that proportion of the probe that has annealed to the template (hence its name: Taq polymerase + PacMan). Degradation of the probe releases the fluorophore from it and breaks the close proximity to the quencher, thus relieving the quenching effect and allowing fluorescence of the fluorophore. Hence, fluorescence detected in the real-time PCR thermal cycler is directly proportional to the fluorophore released and the amount of DNA template present in the PCR.
# Real Time Thermal Cycler
A real-time PCR cycler has a lid with built-in fiber optic cables that measure the fluorescence in the reaction tubes (using laser beams for excitation and detection of the fluorescent emission from the fluorophore). Fluorescence intensities are logged and data stored at each PCR cycle, and then used to create amplification plots of ΔRn (fluorescent signal detected - background) vs cycle number to identify the threshold cycle, CT, which is used to quantitatively determine the amount of DNA template present in the PCR. | https://www.wikidoc.org/index.php/TaqMan | |
e74821fea87c98a5af88afc5bc0484fc0cf77f56 | wikidoc | Tarpon | Tarpon
# Overview
Tarpons are large fish of the genus Megalops; one species is native to the Atlantic, and the other to the Indo-Pacific Oceans. They are the only members of the family Megalopidae.
# Species and habitats
The two species of tarpons are Megalops atlanticus (Atlantic tarpon) and the Megalops cyprinoides (Indo-Pacific tarpon). M. atlanticus is found on the western Atlantic coast from Virginia to Brazil, throughout the coast of the Gulf of Mexico, and throughout the Caribbean. Tarpons are also found along the eastern Atlantic coast from Senegal to South Angola. M. cyprinoides is found along the eastern African coast, throughout southeast Asia, Japan, Tahiti, and Australia. Both species are found in both Seawater|saltwater and freshwater habitats, usually ascending rivers to access freshwater marshes. They are able to survive in brackish water, waters of varying pH, and habitats with low dissolved O2 content due to their swim bladders, which they use primarily to breathe. They are also able to rise to the surface and take gulps of air, which gives them a short burst of energy. The habitats of tarpons vary greatly with their developmental stages. Stage-one larvae are usually found in clear, warm, oceanic waters, relatively close to the surface. Stage-two and -three larvae are found in salt marshes, tidal pools, creeks, and rivers. The habitats are characteristically warm, shallow, dark bodies of water with sandy mud bottoms. Tarpons commonly ascend rivers into freshwater. As they progress from the juvenile stage to adulthood, they move back to the open waters of the ocean, though many remain in freshwater habitats.
# Physical characteristics
Tarpons grow to about 4–8 ft long and weigh 60–280 lbs. They have dorsal and anal soft rays and have bluish or greenish backs. Tarpons possess distinctive lateral lines and have shiny, silvery scales that cover most of their bodies, excluding the head. They have large eyes with adipose eyelids and broad mouths with prominent lower jaws that jut out farther than the rest of the face.
# Biology and behaviour
Tarpons jump up out of the water about four times when hooked making them very challenging to catch. These behaviors can also be damaging to anglers before they are hooked as they can also jump without warning.
## Reproduction and life cycle
Tarpons breed offshore in warm, isolated areas. Females have high fecundity and can lay up to 12 million eggs at once. They reach sexual maturity once they are about 75–125 cm in length. Spawning usually occurs in late spring to early summer.
Their three distinct levels of development usually occur in varying habitats. The first stage, the leptocephalus stage, or stage one, is completed after 20–30 days. It takes place in clear, warm oceanic waters, usually within 10–20 m of the surface. The leptocephalus shrinks as it develops into a larva; the most shrunken larva, stage two, develops by day 70. This is due to a negative growth phase followed by a sluggish growth phase. By day 70, the juvenile growth phase, stage three, begins and the fish begins to rapidly grow until it reaches sexual maturity.
## Diet
Stage-one developing Megalops does not forage for food, but instead absorbs nutrients from seawater using integumentary absorption. Stage-two and -three juveniles feed primarily on zooplankton, but also feed on insects and small fish. As they progress in juvenile development, especially those developing in freshwater environments, their consumption of insects, fish, crabs, and grass shrimp increases. Adults are strictly carnivorous and feed on midwater prey; they swallow their food whole and hunt nocturnally.
## Predation
The main predators of Megalops during stage one and early stage-two development are other fish, depending on their size. Juveniles are subject to predation by other juvenile Megalops and piscivorous birds. They are especially vulnerable to birds when they come to the surface for air, due to the rolling manner in which they move to take in air, as well as the silver scales lining their sides. Adults occasionally fall prey to sharks, porpoises, crocodiles and alligators.
## Swim bladder
One of the unique features of Megalops is the swim bladder, which functions as a respiratory pseudo-organ. These gas structures can be used for buoyancy, as an accessory respiratory organ, or both. In Megalops, this unpaired air-holding structure arises dorsally from the posterior pharynx. Megalops uses the swim bladder as a respiratory organ and the respiratory surface is coated with blood capillaries with a thin epithelium over the top. This is the basis of the alveolar tissue found in the swim bladder, and is believed to be one of the primary methods by which Megalops “breathes”. These fish are obligate air breathers, and if they are not allowed to access the surface, they will die. The exchange of gas occurs at the surface through a rolling motion that is commonly associated with Megalops sightings. This “breathing” is believed to be mediated by visual cues, and the frequency of breathing is inversely correlated to the dissolved O2 content of the water in which they live.
# Megalops and humans
Megalops is considered one of the great saltwater game fishes. They are prized not only because of their great size, but also because of the fight they put up and their spectacular leaping ability. They are bony fish and their meat is not desirable, so most are released after they are caught. Numerous tournaments around the year are focused on catching tarpon.
# Geographical distribution and migration
Since tarpons are not commercially valuable as a food fish, very little has been documented concerning their geographical distribution and migrations. They inhabit both sides of the Atlantic Ocean, and their range in the eastern Atlantic has been reliably established from Senegal to the Congo. Tarpons inhabiting the western Atlantic are principally found to populate warmer coastal waters primarily in the Gulf of Mexico, Florida, and the West Indies. Nonetheless, tarpons are regularly caught by anglers at Cape Hatteras and as far as Nova Scotia, Bermuda, and south to Argentina. Scientific studies indicate schools of tarpons have routinely migrated through the Panama Canal from the Atlantic to the Pacific and back for over 70 years. However, they have not been found to breed in the Pacific Ocean. Nevertheless, anecdotal evidence by tarpon fishing guides and anglers would tend to validate this notion, as over the last 60 years, many small juvenile tarpon, as well as mature giants, have been caught and documented principally on the Pacific side of Panama at the Bayano River, the Gulf of San Miguel and its tributaries, Coiba Island in the Gulf of Chiriquí, and Piñas Bay in the Gulf of Panama. Since tarpons tolerate wide ranges in salinity throughout their lives and will eat almost anything dead or alive, their migrations seemingly are only limited by water temperatures.
Tarpons prefer water temperatures of 72 to 82°F (22 to 28°C); below 60°F (15.6°C) degrees they become inactive, and temperatures under 40°F (4.5°C) can be lethal. | Tarpon
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Tarpons are large fish of the genus Megalops; one species is native to the Atlantic, and the other to the Indo-Pacific Oceans. They are the only members of the family Megalopidae.
# Species and habitats
The two species of tarpons are Megalops atlanticus (Atlantic tarpon) and the Megalops cyprinoides (Indo-Pacific tarpon). M. atlanticus is found on the western Atlantic coast from Virginia to Brazil, throughout the coast of the Gulf of Mexico, and throughout the Caribbean. Tarpons are also found along the eastern Atlantic coast from Senegal to South Angola.[1] M. cyprinoides is found along the eastern African coast, throughout southeast Asia, Japan, Tahiti, and Australia. Both species are found in both Seawater|saltwater and freshwater habitats, usually ascending rivers to access freshwater marshes.[2] They are able to survive in brackish water, waters of varying pH, and habitats with low dissolved O2 content due to their swim bladders, which they use primarily to breathe. They are also able to rise to the surface and take gulps of air, which gives them a short burst of energy. The habitats of tarpons vary greatly with their developmental stages. Stage-one larvae are usually found in clear, warm, oceanic waters, relatively close to the surface. Stage-two and -three larvae are found in salt marshes, tidal pools, creeks, and rivers. The habitats are characteristically warm, shallow, dark bodies of water with sandy mud bottoms. Tarpons commonly ascend rivers into freshwater. As they progress from the juvenile stage to adulthood, they move back to the open waters of the ocean, though many remain in freshwater habitats.[3][4]
# Physical characteristics
Tarpons grow to about 4–8 ft long and weigh 60–280 lbs. They have dorsal and anal soft rays and have bluish or greenish backs. Tarpons possess distinctive lateral lines and have shiny, silvery scales that cover most of their bodies, excluding the head. They have large eyes with adipose eyelids and broad mouths with prominent lower jaws that jut out farther than the rest of the face.[1][2][3]
# Biology and behaviour
Tarpons jump up out of the water about four times when hooked making them very challenging to catch. These behaviors can also be damaging to anglers before they are hooked as they can also jump without warning.
## Reproduction and life cycle
Tarpons breed offshore in warm, isolated areas. Females have high fecundity and can lay up to 12 million eggs at once. They reach sexual maturity once they are about 75–125 cm in length. Spawning usually occurs in late spring to early summer.[3]
Their three distinct levels of development usually occur in varying habitats. The first stage, the leptocephalus stage, or stage one, is completed after 20–30 days. It takes place in clear, warm oceanic waters, usually within 10–20 m of the surface. The leptocephalus shrinks as it develops into a larva; the most shrunken larva, stage two, develops by day 70. This is due to a negative growth phase followed by a sluggish growth phase. By day 70, the juvenile growth phase, stage three, begins and the fish begins to rapidly grow until it reaches sexual maturity.[1][5]
## Diet
Stage-one developing Megalops does not forage for food, but instead absorbs nutrients from seawater using integumentary absorption. Stage-two and -three juveniles feed primarily on zooplankton, but also feed on insects and small fish. As they progress in juvenile development, especially those developing in freshwater environments, their consumption of insects, fish, crabs, and grass shrimp increases. Adults are strictly carnivorous and feed on midwater prey; they swallow their food whole and hunt nocturnally.[3][4]
## Predation
The main predators of Megalops during stage one and early stage-two development are other fish, depending on their size. Juveniles are subject to predation by other juvenile Megalops and piscivorous birds. They are especially vulnerable to birds when they come to the surface for air, due to the rolling manner in which they move to take in air, as well as the silver scales lining their sides.[6] Adults occasionally fall prey to sharks, porpoises, crocodiles and alligators.
## Swim bladder
One of the unique features of Megalops is the swim bladder, which functions as a respiratory pseudo-organ. These gas structures can be used for buoyancy, as an accessory respiratory organ, or both. In Megalops, this unpaired air-holding structure arises dorsally from the posterior pharynx. Megalops uses the swim bladder as a respiratory organ and the respiratory surface is coated with blood capillaries with a thin epithelium over the top. This is the basis of the alveolar tissue found in the swim bladder, and is believed to be one of the primary methods by which Megalops “breathes”. These fish are obligate air breathers, and if they are not allowed to access the surface, they will die. The exchange of gas occurs at the surface through a rolling motion that is commonly associated with Megalops sightings. This “breathing” is believed to be mediated by visual cues, and the frequency of breathing is inversely correlated to the dissolved O2 content of the water in which they live.[3][7]
# Megalops and humans
Megalops is considered one of the great saltwater game fishes. They are prized not only because of their great size, but also because of the fight they put up and their spectacular leaping ability. They are bony fish and their meat is not desirable, so most are released after they are caught. Numerous tournaments around the year are focused on catching tarpon.[8]
# Geographical distribution and migration
Since tarpons are not commercially valuable as a food fish, very little has been documented concerning their geographical distribution and migrations. They inhabit both sides of the Atlantic Ocean, and their range in the eastern Atlantic has been reliably established from Senegal to the Congo. Tarpons inhabiting the western Atlantic are principally found to populate warmer coastal waters primarily in the Gulf of Mexico, Florida, and the West Indies. Nonetheless, tarpons are regularly caught by anglers at Cape Hatteras and as far as Nova Scotia, Bermuda, and south to Argentina. Scientific studies[9] indicate schools of tarpons have routinely migrated through the Panama Canal from the Atlantic to the Pacific and back for over 70 years. However, they have not been found to breed in the Pacific Ocean. Nevertheless, anecdotal evidence by tarpon fishing guides and anglers would tend to validate this notion, as over the last 60 years, many small juvenile tarpon, as well as mature giants, have been caught and documented principally on the Pacific side of Panama at the Bayano River, the Gulf of San Miguel and its tributaries, Coiba Island in the Gulf of Chiriquí, and Piñas Bay in the Gulf of Panama. Since tarpons tolerate wide ranges in salinity throughout their lives and will eat almost anything dead or alive, their migrations seemingly are only limited by water temperatures.[citation needed]
Tarpons prefer water temperatures of 72 to 82°F (22 to 28°C); below 60°F (15.6°C) degrees they become inactive, and temperatures under 40°F (4.5°C) can be lethal.[citation needed] | https://www.wikidoc.org/index.php/Tarpon |
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